Ocular Squamous Cell Carcinoma Research Articles

Ocular squamous cell carcinoma: A patho-morphological and AgNOR based diagnosis

A fifteen years old female buffalo was referred to the Teaching Veterinary Clinical Complex (TVCC), RS Pura, Jammu, India with a history of purulent discharge and protruded mass from the right eye with an impaired vision for 30 days. On physical examination, there was ulcerated vesicular growth at the sclera corneal junction. Protruded mass was removed surgically and was taken for histopathological examination and AgNOR count. On histopathological studies, cells displayed severe anaplasia, pleomorphism, hyperchromatic nuclei, multiple nucleoli, and frequent mitotic figures and it was diagnosed as ocular squamous cell carcinoma. The value of mean and proliferative AgNOR for ocular squamous cell carcinoma was found to be 2.83±0.87 and 32%, respectively. Based on patho-morphological examination and AgNOR count, the protruded mass was led to the final diagnosis of ocular squamous cell carcinoma.

Immunotherapy for local/regional control of locally advanced orbital and periocular squamous cell carcinoma.

e18034 Background: Periocular squamous cell carcinoma can be of eyelid skin, ocular surface (bulbar) or palpebral conjunctival, or of lacrimal sac/nasolacrimal duct mucosal origin, is relatively rare, and presents unique anatomic considerations due to proximity to the eye and inherent risk to ocular structures associated with high dose radiation therapy. We herein report on 17 patients with orbital or periocular SCC who were treated with immunotherapy (IO) to decrease surgical morbidity or to avoid high dose radiation therapy. Methods: Retrospective review of all previously unreported patients with orbital, conjunctival, or periocular SCC who were treated with IO either in the neoadjuvant setting prior to surgery or for treatment of periocular SCC with perineural spread into the orbit and skull base. Results: 17 patients, 12 men and 5 women (Age range: 44-92; median=70 years old) with orbital (n=6), conjunctival (n=5), or lacrimal sac/duct (n=2) squamous cell carcinoma (SCC), or periocular SCC with perineural spread into the orbit and skull base (n=4) who were treated with IO either as single drug (n= 11) or in combination with chemotherapy (n= 6 ). In all patients either cemiplimab or pembolizumab was used. In 13 patients IO was used in the neoadjuvant setting prior to planned surgery. In 4 patients with perineural spread as they had non surgically resectable disease, IO was used to avoid high dose radiation therapy with its inherent significant risk of ocular toxicity. Overall, 3 patients achieved complete response, 10 patients achieved partial response, and 4 patients had stable disease, using RECIST criteria. One of 5 patients with conjunctival SCC also had nodal metastasis at presentation and achieved a dramatic complete response of both the conjunctival tumor and the nodal metastasis and managed to avoid surgery altogether. This patient had a very high tumor mutation burden (TMB). One patient developed diabetic ketoacidosis as a side effect of IO; otherwise the adverse effects were low grade. Conclusions: IO either as single drug or in combination with chemotherapy has a fairly high response rate in patients with ocular adnexal, conjunctival or orbital SCC and in patients with periocular SCC with perineural spread in the orbit and skull base. Future prospective trails using IO for orbital and ocular adnexal SCC should be planned and should aim to correlate molecular data such as TMB with response.

The role of oxidative and nitrosative stress in bovine ocular squamous cell carcinomas

Oxidative stress is strongly linked to carcinogenesis, especially head, neck and oral SCCs in humans. In this study, we aimed to evaluate the role of oxidative and nitrosative stress in Bovine ocular squamous cell carcinomas (BOSCCs) using immunohistochemical markers such as Nitrotyrosine (NT), Malondialdehyde (MDA) and 8-hydroxy-2’ -deoxyguanosine (8-OHdG). Tissues were collected from 24 cattle brought to the Pathology Department for routine diagnosis. Tumour samples were fixed in 10% neutral buffered formalin, processed routinely, and embedded in paraffin wax. Tissue sections were cut into 5 μm thickness and stained with Hematoxylin-Eosin to detect histopathological changes. The sections were examined under a light microscope and photographed. The avidin-biotin-peroxidase method was used as immunohistochemical staining. It was observed that the cauliflower-like tumoral masses were mostly located on the upper and lower eyelids, the third eyelid, cornea, limbus, or covering the entire eyeball. NT, MDA and 8-OHdG expressions were statistically increased in poorly-differentiated (PD) cases compared to welldifferentiated (WD) and moderately-differentiated (MD) cases. On the basis of the results of the increase in these markers, we concluded that nitrosative and oxidative stress may have an important role in the carcinogenesis of BOSCCs.

OSSN: An underrated neoplasia of the eye

: Ocular surface squamous cell carcinoma (OSSN) is a general term for various conjunctival tumors, including conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC).: To evaluate the clinico-demographic characteristics and histopathological findings of ocular surface squamous cell carcinoma. : eyes of 47 patients aged 21 to 80 years with conjunctival tumors were included in the study and underwent excisional biopsy and subsequent histopathological examination. : Statistically significant associations were found with age, symptom duration, and lesion size (p<0.05). Benign and preinvasive lesions are more common than invasive lesions.

Equus caballus papillomavirus type 2 (EcPV2)-associated benign penile lesions and squamous cell carcinomas.

Squamous cell carcinoma is the most common genital, ocular and gastric tumour in horses. Equus caballus papillomavirus type 2 (EcPV2) DNA has been detected in several studies in equine penile squamous cell carcinomas (SCCs) and precursor lesions providing evidence of a causal role of EcPV2 in equine genital SCCs. Recently, EcPV2 E6/E7 nucleic acids were also detected in equine gastric SCCs, but further studies are required to determine the role of EcPV2 infection in the pathogenesis of gastric SCC. EcPV2 nucleic acids have been rarely described in ocular SCCs and precursor lesions. To investigate the presence of EcPV2 nucleic acids with polymerase chain reaction (PCR) and in situ hybridisation (ISH) in penile hyperplasias, papillomas and SCCs in horses and to determine whether EcPV2 nucleic acids can be detected in SCCs affecting other locations, including the stomach, ocular tissues and larynx. Twenty-one archival formalin-fixed paraffin embedded (FFPE) tissue samples, including 12 genital lesions comprising penile hyperplasias, papillomas and SCCs, 6 ocular SCCs, 2 gastric SCCs and 1 laryngeal SCC, were screened by PCR and ISH for EcPV2 E6/E7 DNA and mRNA. Archival FFPE tissue samples (eyelid and penile mucosa and preputium) from six horses without a diagnosis or history of neoplastic or papillomavirus-associated disease were included as controls. EcPV2 nucleic acids were detected by PCR and ISH in all genital lesions (12/12) and gastric SCCs (2/2), in two ocular SCCs (2/6) and in one laryngeal SCC (1/1). In control horses, one eyelid sample was positive in PCR but not in ISH. The remaining control samples were negative for EcPV2 E6/E7 nucleic acids in PCR and ISH. These results further support the role of EcPV2 infection in the development of equine genital SCCs and suggest that EcPV2 infection may also act as a predisposing factor for other SCCs in horses, including gastric, ocular and laryngeal SCCs.

Bovine ocular squamous cell carcinoma of cattle: A case report

Bovine ocular squamous cell carcinoma of cattle: A case report

Sinus trephination and horn problems

Conditions of the head requiring surgery in cattle are not un­common when considering the incidence of conditions such as ocular squamous cell carcinoma, surgical dehorning, sinusitis and trauma-related injury. Surgery involving the eyes in cattle is relatively common, whereas surgery of the paranasal sinuses is less common. Surgery for conditions of the head tend to have a more favorable prognosis when there is early intervention.

Immune Checkpoint Inhibitor Therapy for Orbital and Ocular Adnexal Squamous Cell Carcinomas: International Society of Ocular Oncology President's Lecture, 2022.

To summarize an invited lecture topic from the proceedings of the International Society of Ocular Oncology meeting in Leiden in 2022. Mechanism of action, indications, and the authors' clinical experience with immune checkpoint inhibitors in patients with locally advanced ocular adnexal squamous cell carcinoma are summarized. Several cases of locally advanced conjunctival, eyelid, and lacrimal sac/duct squamous cell carcinoma that were successfully treated with immune checkpoint inhibitors (PD-1 directed) are shared. Immune checkpoint inhibitors are effective at reducing tumor size and enabling eye-preserving surgery in patients with locally advanced ocular adnexal squamous cell carcinoma with orbital invasion. They present a new strategy for the treatment of locally advanced squamous cell carcinoma of the ocular adnexa and orbit.

Relative and Quantitative Characterization of the Bovine Bacterial Ocular Surface Microbiome in the Context of Suspected Ocular Squamous Cell Carcinoma.

The ocular surface microbiome is altered in certain disease states. The aim of this study was to characterize the bovine bacterial ocular surface microbiome (BBOSM) in the context of ocular squamous cell carcinoma (OSCC). The conjunctiva of normal (n = 28) and OSCC (n = 10) eyes of cows aged 2 to 13 years from two farms in Louisiana and Wyoming were sampled using individual sterile swabs. DNA extraction followed by 16S ribosomal ribonucleic acid (rRNA) gene sequencing and real-time polymerase chain reaction (RT-PCR) were performed to, respectively, assess the relative and absolute BBOSM. Discriminant analysis (DA) was performed using RT-PCR data, and relative abundance analysis was performed using 16S rRNA gene sequencing data. The 11 most abundant phyla in both normal and OSCC-affected cows were identified using 16S rRNA gene sequencing analysis. The relative abundance of Euryarchaeota was found to be significantly lower (p = 0.0372) in OSCC eyes compared to normal eyes. Relative abundance differences within and between geographic locations were also identified. Quadratic DA categorized samples as OSCC or normal with 100% sensitivity and 83.3-100% specificity. Relative abundance analysis identified relative BBOSM phylum alterations in OSCC. Quadratic DA can be used to accurately categorize BBOSM from normal and OSCC ocular surface samples.

Detection of Equine Papillomaviruses and Gamma-Herpesviruses in Equine Squamous Cell Carcinoma.

Squamous cell carcinoma (SCC) seriously compromises the health and welfare of affected horses. Although robust evidence points to equine papillomavirus type 2 (EcPV2) causing genital lesions, the etiopathogenesis of equine SCC is still poorly understood. We screened a series of SCCs from the head-and-neck (HN), (peri-)ocular and genital region, and site-matched controls for the presence of EcPV2-5 and herpesvirus DNA using type-specific EcPV PCR, and consensus nested herpesvirus PCR followed by sequencing. EcPV2 DNA was detected in 45.5% of HN lesions, 8.3% of (peri-)ocular SCCs, and 100% of genital tumors, whilst control samples from tumor-free horses except one tested EcPV-negative. Two HNSCCs harbored EcPV5, and an ocular lesion EcPV4 DNA. Herpesvirus DNA was detected in 63.6%, 66.6%, 47.2%, and 14.2% of horses with HN, ocular, penile, and vulvar SCCs, respectively, and mainly identified as equine herpesvirus 2 (EHV2), 5 (EHV5) or asinine herpesvirus 5 (AsHV5) DNA. In the tumor-free control group, 9.6% of oral secretions, 46.6% of ocular swabs, 47% of penile samples, and 14.2% of vaginal swabs scored positive for these herpesvirus types. This work further highlights the role of EcPV2 as an oncovirus and is the first to provide information on the prevalence of (gamma-)herpesviruses in equine SCCs.

An investigation of bovine papillomaviruses from ocular squamous cell carcinomas in cattle.

Ocular squamous cell carcinomas (OSCCs) in cattle has been studied for many years, but no definite etiology has been established. Squamous cell carcinomas (SCCs) may occur in different body parts of cattle. Depending on the location, it can cause an economic loss of varying degrees. The aim of this study was to investigate the causes of OSCCs in the eye region of cattle. Methods: Sixty tumoral masses taken form 60 cattle with proliferation in the eye region that were collected between the years 2012-2022 were used. These cases were admitted to our department for routine diagnosis. The tissues were diagnosed as OSCC using histopathological methods. The presence of bovine papillomavirus (BPV), one of the causative factors, was investigated using immunohistochemical and polymerase chain reaction (PCR). Macroscopically masses were nodular or cauliflower-like and fragile and had hemorrhagic surfaces. Considering the keratin pearls, tumoral islands, and squamous differentiation, 20 out of 60 cases were classified as well, 20 as moderately, and 20 as poorly-differentiated OSCCs. 47 of the 60 cases were BPV positive using immunohistochemical methods. However, BPV nucleic acid was detected in only two cases with PCR. Only one of the cases could be sequenced. After phylogenetic analysis, virus strain was identified as BPV-1. Our results indicated that papillomaviruses can contribute to the development of OSCCs, in both precursor lesions and also advanced stage OSCCs. We found that BPV-1 has a possible causative role; however, more studies are needed to investigate the role of other viral agents and their interaction with secondary factors.

Ocular squamous cell carcinoma in a buffalo

Ocular squamous cell carcinoma in a buffalo

Eye enucleation and exenteration in -cattle: a retrospective study of 38 cases (2013-2020).

The study aimed to describe clinical indications for eye enucleation and exenteration, the occurrence of complications and long-term outcome in cattle, and examine owners' attitude towards enucleation and exenteration and their satisfaction with the surgical outcome. Medical records from the two veterinary teaching hospitals in Switzerland were reviewed to identify cattle that underwent unilateral enucleation or exenteration between January 2013 and December 2020. Data extracted included medical history, ocular examination, clinical diagnosis, surgical procedure including anesthesia, suture material and pattern used, complications, and treatment thereof. Long-term follow-up was evaluated via national animal database inquiries to determine survival time and via owners' interviews with the use of a standardized questionnaire that included questions regarding the occurrence of complications and reason for culling, production performances and perceived quality of life after surgery, concerns, factors affecting the decision to proceed with surgery, and general satisfaction with the outcome. Descriptive statistics, Fisher's exact tests and unpaired t-test were used to summarize the data and assess association between variables. Association was considered significant if p < 0,05. Thirty-eight cases were identified, with a median age of 5 years. More than half of the cases (55,3 %) were diagnosed with non-neoplastic ocular lesions represented by severe trauma with loss of globe content, globe rupture with history of infectious keratoconjunctivitis or hypopyon, or congenital malformations. The remaining cases were diagnosed with neoplastic lesions, including ocular squamous cell carcinoma (OSCC), melanoma, or sarcoma. Complications following surgery were reported in 29 % of cases and included postoperative infection and recurrence of OSCC. There was no significant association between ocular diagnosis and the occurrence of postoperative complications or survival time. Surgery did not seem to influence the animals' postoperative production performance or the perceived quality of life. Most owners (92 %) were satisfied with the surgical outcome. The occurrence of postoperative complications leading to increased overall costs and culling was the main reason for lower owner satisfaction.

Identification of Long Noncoding RNAs Involved in Eyelid Pigmentation of Hereford Cattle.

Several ocular pathologies in cattle, such as ocular squamous cell carcinoma and infectious keratoconjunctivitis, have been associated with low pigmentation of the eyelids. The main objective of this study was to analyze the transcriptome of eyelid skin in Hereford cattle using strand-specific RNA sequencing technology to characterize and identify long noncoding RNAs (lncRNAs). We compared the expression of lncRNAs between pigmented and unpigmented eyelids and analyzed the interaction of lncRNAs and putative target genes to reveal the genetic basis underlying eyelid pigmentation in cattle. We predicted 4,937 putative lncRNAs mapped to the bovine reference genome, enriching the catalog of lncRNAs in Bos taurus. We found 27 differentially expressed lncRNAs between pigmented and unpigmented eyelids, suggesting their involvement in eyelid pigmentation. In addition, we revealed potential links between some significant differentially expressed lncRNAs and target mRNAs involved in the immune response and pigmentation. Overall, this study expands the catalog of lncRNAs in cattle and contributes to a better understanding of the biology of eyelid pigmentation.

Immunohistochemical and mutational status of telomerase reverse transcriptase in conjunctival squamous cell carcinoma.

Purpose:Mutations in human telomerase reverse transcriptase (TERT) are associated with increased telomerase activity in cutaneous melanomas. Conjunctival squamous cell carcinoma, also referred to as ocular surface squamous cell carcinoma, is cancer on the surface of the eye. Recent studies have identified UV signature mutations in TERT promoters in ocular melanoma and ocular surface squamous neoplasia. However, its immunohistochemical status has not been reported in ocular surface squamous cell carcinoma. This study aimed to explore the immunohistochemical and mutational status of TERT in ocular surface SCC.Methods:The immunohistochemical expression of TERT and mutational status of TERT promoter was evaluated in 19 ocular surface squamous cell carcinoma cases. Conjunctival melanoma tissue was used as a positive control.Results:The cytoplasmic overexpression of TERT was detected in 11/19 (57%), and TERT promoter mutations were identified in 6/19 (31%) of ocular surface squamous cell carcinoma. Out of these, 66% had a C228T mutation, and 33% had a C250T mutation. The TERT expression was found to be associated with a high (≥T3) AJCC category (P = 0.023), and TERT immunoexpression was significantly correlated with reduced disease-free survival (P = 0.024, log-rank analysis) in ocular surface squamous cell carcinoma patients.Conclusion:The present study demonstrates that TERT promoter mutations with UV signatures are frequent in ocular surface squamous cell carcinoma. The increased expression of TERT could be of biological significance in aggressive ocular surface squamous cell carcinoma.

Surgical management and mitomicin adjunct therapy for ocular squamous cell carcinoma in Cow

Surgical management and mitomicin adjunct therapy for ocular squamous cell carcinoma in Cow

Current Status of Bovine Ocular Squamous Cell Carcinoma

Bovine ocular squamous cell carcinoma (BOSCC) is one of the important malignant neoplasms of cattle arising from squamous epithelium. The tumour was recorded at the age of three to eight years, and it affects most countries of the world. The possible etiologies include ultraviolet radiation, exposure to sunlight, nutrition, lack of pigmentation, bovine papilloma virus, increased altitude, decreased latitude, and hereditary and outdoor farming systems. Breeds of Hereford, Holstein, Jersey, Holstein cross and Jersey cross cattle are mostly affected, Common sites of the lower eyelid, third eyelid, limbus corneoscleral junction and cornea conjunctival junction were reported. Grossly the tumour is having plague, keratoma, papilloma and carcinoma formation. Cytological and histopathological appearance of BOSCC categorized as poorly differentiated squamous cell carcinoma, moderately squamous cell carcinoma and well differentiated squamous cell carcinoma. Immunohistochemistry using cytokeratin, MNF116, involucrin, P53, ki67 are the useful markers of BOSCC. Surgical extirpation is the choice of management of BOSCC and continued exposure to sunlight to be avoided to control this BOSCC.

Prognostic significance of PCNA, MMP-9 and p53 in bovine ocular squamous cell carcinomas

In this study, we aimed to evaluate PCNA, MMP-9 and p53 expressions according to differentiation degree of BOSCCs by immunohistochemical methods. The material of this study was composed of BOSCC biopsy samples taken from 30 cattle brought to our department. Tissue samples from cattles were fixed in 10% buffered formaldehyde solution, processed routinely, embedded in paraffin and sectioned at 5μm and stained with Hematoxylin &amp; Eosine in order to detect histopathological changes. Sections were examined and photographed under a light microscope. Avidin-Biotin Peroxidase method was used as immunohistochemical method. We observed that the masses were nodular and cauliflower-like appearance. We found that the surfaces of the masses were highly hemorrhagic and ulcerative, sometimes covered with a purulent discharge. We defined cases with excessive and large numbers of keratin pearls, large tumoral islands, and evident squamous differentiation were defined as well-differentiated. In moderately-differentiated cases, we found that the number and size of keratin pearls decreased compared to well-differentiated cases. In addition, we observed that tumoral islets were smaller in these cases, similar to keratin pearls, and the number of poorly differentiated tumor cells increased. In poorly-differentiated cases, we determined that keratinization was either absent or formed in individual cells. As a result of statistical analysis, there was no statistically significant difference between good, moderate and poorly differentiated cases in terms of PCNA and MMP-9 expressions, but we found that the increase in p53 expression correlated with the degree of differentiation of the tumor. In conclusion, we think that p53 is a useful marker in determining the prognosis of BOSCCs.

A multimodal approach to management of ocular surface squamous cell carcinoma in horses

A multimodal approach to management of ocular surface squamous cell carcinoma in horses

Topical 5‐fluorouracil as an adjunct treatment in equine corneolimbal squamous cell carcinoma

SummaryAn 11‐year‐old crossbreed mare was presented with a nodular, pink mass at the temporal corneolimbal junction of the right eye. Histopathology confirmed the diagnosis of invasive squamous cell carcinoma. The mare underwent lamellar keratectomy and conjunctivectomy under general anaesthesia, followed by adjunctive topical chemotherapy with 1% 5‐fluorouracil solution for 10 days post‐operatively. Adverse effects included moderate conjunctival inflammation and exuberant granulation tissue formation at the surgical site, responding to surgical debulking and topical corticosteroid application. No mass regrowth was present at 12 months following discharge. This report describes the successful use of topical 1% 5‐FU as an adjunctive treatment for equine ocular squamous cell carcinoma.