Ocular Surface Squamous Neoplasms Research Articles

OVOL1 immunohistochemical expression is a useful tool to diagnose invasion in ocular surface squamous neoplasms

Background and objectivesOVOL1 is a gene that negatively regulates mesenchymal transformation, which allows epithelial cells to invade the stroma. On the other hand, it negatively regulates c-Myc, which has a positive effect on cell proliferation. The aim of this study is to evaluate the expression of OVOL1 and c-Myc in ocular surface squamous neoplasia (OSSN). Patients and methodsCross-sectional cohort study of 36 samples including 6 squamous papillomas, 19 conjunctival intraepithelial neoplasms, 6 squamous carcinomas and 7 normal conjunctivae were evaluated using immunohistochemistry against OVOL1 and c-Myc. The expression of both markers was analysed using the H-score (intensity 1–3 multiplied by the percentage of positive cells). ResultsPercentages of 98 and 100 of the OSSN, and 57 and 71% of the normal conjunctivae expressed OVOL1 and c-Myc respectively, however, the mean H-score of OVOL1 and c-Myc was higher in the OSSN than in normal conjunctivae group (P=0.0001 in both). Within the OSSN, OVOL1 demonstrated a higher H-score in the conjunctival intraepithelial neoplasms and papilloma, compared to the squamous carcinoma (P<0.01) group. c-Myc did not show differences between the OSSN groups. An H-score lower than 35 differentiates a squamous cell carcinoma from other OSSN lesions with a sensitivity of 83.3% and a specificity of 100%. ConclusionsThe expression of OVOL1 is a useful tool to differentiate between a squamous carcinoma of conjunctival intraepithelial neoplasms and papilloma. OVOL1 could play a role in the invasiveness of squamous neoplasms and places it as a potential therapeutic target.

A Rare Case Report of Invasive Ocular Surface Squamous Neoplasm of Conjunctiva

Ocular surface neoplasm(OSSN) represent a rare but broad spectrum of disease, including mild dysplasia on one end of the spectrum and invasive Squamous cell carcinoma(SCC) on the other. Thus, the diagnosis completely depends on histopathological examination of the lesion. The incidence of ocular surface neoplasia is strongly associated with factors like solar ultraviolet radiation, HIV and human papilloma virus(HPV) infections. Most lesions occur at the limbus within the interpalpebral fissure particularly the nasal side. Their importance lies in the fact that they mimic benign lesions like pterygium or even chronic conjunctivitis and thus can be misinterpreted and inadequately treated. Red eye and ocular irritation are the most common presenting symptoms. No tumor related deaths or metastasis are generally seen. Surgery with intra-operative control of surgical margins and adjunctive chemotherapy, immunotherapy and cryotherapy result in good tumor control rates, with promising results in aggressive, recurrent and large tumors.

P16 Expression Correlates with Invasive Ocular Surface Squamous Neoplasms in HIV-Infected Mozambicans

Background: p16 immunohistochemistry is widely used to diagnose human papillomavirus (HPV)-related squamous neoplasms of cervix, anogenital, head, and neck tissues. The incidence of these HPV-related squamous neoplasms is markedly increased in the HIV-infected population. Ocular surface squamous neoplasia (OSSN) is also more common in HIV-infected patients. However, the expression pattern of p16 in OSSN among HIV-infected patients is unclear. Here, we examined the expression of p16 in OSSN surgical excisions collected from a large HIV-infected cohort from ­Mozambique. Methods: OSSN surgical tissue specimens were collected from 75 Mozambican patients. Formalin-fixed, paraffin-embedded tissue blocks from these OSSNs were sectioned, stained with hematoxylin and eosin (H&E), and p16 expression by immunohistochemistry. H&E slides were reviewed to determine if OSSNs were noninvasive conjunctival intraepithelial neoplasms or invasive squamous cell carcinomas (SCC). Cases were classified as p16 positive or negative based on diffuse nuclear and cytoplasmic expression of p16 in neoplastic cells. Results: p16 positivity was found in a minority of OSSN cases (14/75). p16 positivity was significantly associated with the invasive SCC type of OSSN in HIV-infected patients (p value of 0.026). Conclusions: The majority of OSSNs in our HIV-infected cohort do not express p16. However, those cases that are p16-positive are significantly more likely to be the invasive SCC form of OSSN. We propose that p16 expression may identify more aggressive OSSNs in HIV-infected populations.

Ocular surface squamous neoplasms: A case series

Neoplastic lesions of conjunctival and corneal squamous epithelium known as ocular surface epithelial dysplasia range from mild dysplasia, carcinoma in situ to invasive squamous cell carcinoma. Ocular surface squamous neoplasia (OSSN) has a predilection for mitotically active corneoscleral limbus (95%). The incidence of OSSN varies between 0.02 and 3.5/100,000 populations. The most frequent to be affected by these neoplasms are the elderly males of fifth to sixth decade. We highlight case series of five patients presenting with ocular surface neoplasms of which two were immunocompromised. The diagnosis of the few cases was made on cytology and confirmed on histopathology. These cases are discussed to emphasize on the increased incidence of these ocular surface neoplasms.

Exfoliative Cytology in the Diagnosis of Ocular Surface Squamous Neoplasms.

Surface tumors of the eye comprise an ample spectrum of diseases with various clinical manifestations. Diagnosis has been traditionally achieved through core biopsies, but cytology is an innovative, fast, and minimally invasive method. The objective of this study was to investigate the use of exfoliative cytology as an alternative method for the detection of ocular surface squamous neoplasm (OSSN). Exfoliative cytology of the lesions was performed by collecting smears using plastic brushes followed by smearing the cells onto slides and subsequently fixing them in 90% alcohol. Incisional biopsies were performed at the exact same location and sent for processing in 10% formaldehyde. Both the surgical pathologist and cytopathologist were masked to the clinical characteristics and to the corresponding cytological or histological result. Twenty-two patients were enrolled in the study (12 men and 10 women, median age 52.5 years). Final histological diagnoses comprised 7 cases of pterygium, 7 squamous-cell carcinomas, 4 squamous papillomas, and 4 chronic inflammatory processes. Cytohistological agreement was achieved in 19 (86.4%) of the samples. Cytology showed a sensitivity, specificity, positive predictive value, and negative predictive value of 85.7%, 86.7%, 75%, and 92.9%, respectively, in detecting OSSN. Exfoliative cytology of the conjunctival lesions is a simple procedure, with high agreement to the histological follow-up. Its broad use could augment the early diagnosis of OSSN, with improvement in patient prognosis.

Differential Expression of Stem Cell Markers in Ocular Surface Squamous Neoplasia.

Ocular Surface Squamous Neoplasm (OSSN) is the neoplasia arising from the conjunctiva, cornea and limbus. OSSN ranges from mild, moderate, severe dysplasia, carcinoma in situ (CIS) to squamous cell carcinoma (SCC). Recent findings on cancer stem cells theory indicate that population of stem-like cell as in neoplasia determines its heterogeneity and complexity leading to varying tumor development of metastatic behavior and recurrence. Cancer stem cell markers are not much explored in the cases of OSSN. In the present study, we aim to evaluate the expression of stem cells using stem cell markers mainly p63, ABCG2, c-KIT (CD117) and CD44 in OSSN tissue, which could have prognostic significance. The present study tries for the first time to explore expression of these stem markers in the cases of OSSN. These cases are subdivided into two groups. One group comprises of carcinoma in situ (n = 6) and the second group comprises of invasive carcinoma (n = 6). The mean age at presentation was 52 years; with 53 years for CIS group and 52 years for SCC group. From each group section from the paraffin block were taken for the IHC staining of p63, c-Kit, ABCG2 and CD44. Our experiments show high expression of P63 and CD44 in the cases of CIN and SCC. Both CIS and SCC displayed positive staining with p63, with more than 80% cells staining positive. However minimal expression of c-kit in both CIN and SCC. But surprisingly we got high expression of ABCG2 in cases of carcinoma in situ as compared to that of invasive squamous cell carcinoma. More than 50% of cells showed CD44 positivity in both CIS and SCC groups. Our results show for the first time that these four stem cells especially the limbal epithelium stem cells play a vital role in the genesis of OSSN but we need to explore more cases before establishing its clinical and biological significance.

Elevated expression of ABCB5 in ocular surface squamous neoplasia.

ATP-binding cassette subfamily B member 5 (ABCB5) is a new member of the ATP-binding cassette superfamily and has been reported as a novel marker for limbal stem cell (LSC), which is essential for corneal homeostasis. ABCB5 expression has also been discovered in the subpopulation of several cancer cells containing the cancer stem cell (CSC). However, the pathogenetic relationship between LSC and CSC and ABCB5 in the ocular surface squamous neoplasm (OSSN) is still entirely unknown. To improve understanding of the role of ABCB5 in OSSN, we performed immunohistochemistry for ABCB5 in nine OSSN case series. While expression of ABCB5 is restricted to the basal epithelial cell layer in the normal limbus, elevated expressions of ABCB5 were clearly observed in all OSSN, and there was some breadth in the range of intensity of ABCB5 expression. Interestingly, the elevated expression patterns of ABCB5 in OSSN could be classified in three categories: perivascular, marginal and diffuse patterns. Our findings demonstrated for the first time that the expression of ABCB5 was upregulated in OSSN and that elevated expression of ABCB5 may be involved in the pathogenesis of OSSN.

A case of conjunctival mucoepidermoid carcinoma in Australia

Conjunctival mucoepidermoid carcinoma is a very rare but highly aggressive conjunctival neoplasm with 42 previously reported cases. We report the case of a 56-year-old male with a left ocular surface squamous neoplasm, which was subsequently treated with excision and autoconjunctival graft. Histopathology of the operative specimen reported a low-grade conjunctival mucoepidermoid carcinoma, and the patient was then treated with an adjunctive course of mitomycin C. On review 10 months after lesion excision, there was no recurrence, and the patient was otherwise well. Due to its rare incidence, difficult clinical diagnosis, and accompanying poor prognosis, conjunctival mucoepidermoid carcinoma should always be considered in the differential diagnosis of conjunctival neoplasms, and full histopathologic examination, including mucin-staining techniques, of all suspicious conjunctival biopsies should occur.

Clinicopathologic Correlation of Ocular Surface Squamous Neoplasms at Bascom Palmer Eye Institute: 2001 to 2010

To describe the clinical and histologic characteristics of ocular surface squamous neoplasia (OSSN) lesions and provide clinicopathologic correlation to determine clinical features that may indicate higher-grade lesions. Retrospective case series. A total of 612 consecutive OSSN lesions sent to the Bascom Palmer ocular pathology laboratory from January 1, 2001 to September 20, 2010. Pathologic examination of lesions by a single experienced ocular pathologist (S.R.D.). Review of pathology records and patient charts. Correlation of clinical factors and histology of higher-grade OSSN. Over the studied period, 33% of submitted specimens were characterized as mild, moderate, or severe dysplasia; 52% were classified as carcinoma in situ; and 11% were graded as squamous cell carcinoma. Characteristics associated with higher-grade OSSN lesions included male gender, biopsy at Bascom Palmer Eye Institute, temporal and superior locations, lack of corneal involvement, papillomatous and nodular appearance, microscopic multifocality, and positive margins on biopsy. Certain clinical factors are associated with higher-grade histologic lesions. These findings may help clinicians more accurately evaluate and anticipate the pathologic grade of conjunctival and corneal lesions suspected to be OSSN.

Predictors of Ocular Surface Squamous Neoplasia Recurrence after Excisional Surgery

To identify predictors of ocular surface squamous neoplasm (OSSN) recurrence after operative resection. Retrospective case series. Three hundred eighty-nine consecutive patients who underwent excisional biopsy for OSSN lesions at the Bascom Palmer Eye Institute from January 1, 2001, to September 20, 2010. Review of pathology records and patient charts. Identification of factors predictive of OSSN recurrence. Of 389 excised OSSN lesions, 44 recurred during follow-up. The 1-year recurrence rate was 10% and the 5-year recurrence rate was 21%, with a mean time to recurrence in those with a recurrence of 2.5 years (standard deviation, 3.4). Using the American Joint Committee on Cancer (AJCC) clinical staging system, T3 and T2 lesions portended a higher risk of recurrence compared with T1 (T2/T1 hazard ratio [HR], 2.05 [P = 0.04]; T3/T1 HR, 2.31 [P = 0.07]). In addition, a location characteristic that increased the risk of tumor recurrence was tarsal involvement (AJCC T3 stage lesion; HR, 4.12; P = 0.007). Nasal location was associated with a decreased risk of tumor recurrence (HR, 0.41; P = 0.008). Pathologic characteristics significantly associated with tumor recurrence were the presence of positive margins (HR, 2.73; P = 0.008) and higher grade lesions (carcinoma in situ and squamous cell carcinoma versus dysplasia; HR, 2.55; P = 0.02). Treatment with adjuvant cryotherapy significantly decreased the risk of tumor recurrence (HR, 0.51; P = 0.03). In those patients with positive margins, the use of postoperative topical interferon therapy lowered the recurrence rate to a level similar to that of patients with negative margins. Certain patient and tumor factors are associated with a higher risk of OSSN recurrence after operative excision, such as tarsal tumor location and positive surgical margins. Postoperative adjuvant therapy should be considered in patients with high-risk OSSN characteristics.

A historical perspective of registered cases of malignant ocular tumors in Zimbabwe (1990 to 1999). Is HIV infection a factor?

Anecdotal and published reports suggest that ocular tumours are on the increase in Zimbabwe. To determine the trends in incidence rates of common malignant ocular tumours registered with the Zimbabwe Cancer Registry during the last decade (1990 to 1999). Retrospective study. Data were collected from the Zimbabwe National Cancer Registry, the Zimbabwe National Census 1992 and 2002 Reports, and patient records from hospitals. All cases of malignant ocular tumours registered with the Zimbabwe National Cancer Registry between 1 January 1990 and 31 December 1999. Age standardized annual incidence rates for registered cases of common ocular tumours. The age-adjusted annual incidence rates of squamous cell carcinoma of the conjunctiva had a more than 10-fold increase from 0.17 to 1.8 per 100,000 people during periods 1990 and 1999 respectively. Retinoblastoma dropped by more than half from 0.8 to 0.34 per 100,000 during the same period. The annual age standardised incidence rates for all ocular tumours showed a significant upward linear trend (chi2: 362.78, df=9 and p < 0.001). There was no significant gender difference in the distribution of these tumours amongst the study population. The increasing trend in the age-adjusted annual incidence rates of ocular surface squamous neoplasms could be attributed to the worsening HIV and AIDS pandemic in Zimbabwe or improved access/utilization of health services by the public.

Preoperative Brush and Impression Cytology in Ocular Surface Squamous Neoplasms

Preoperative cytologic diagnoses of ocular surface squamous neoplasms were evaluated and compared with histologic diagnoses. Impression cytology (Millipore filter paper) and brush cytology were applied to 32 patients who had conjunctival neoplasms. Papanicolaou-stained cytologic preparations and hematoxylin and eosin-stained histologic sections were examined by light microscopy. The brush technique was used on 27 patients; impression cytology was applied in 5 cases. Cytologic and histologic diagnoses were concordant in 26 cases. Squamous cell carcinoma or carcinoma in situ was diagnosed in 18 and dysplasia in 4 cases. Squamous metaplasia and normal-appearing conjunctival epithelial cells were diagnosed cytologically in four cases; of those histologic diagnoses, one was pterygium and three, conjunctival nevus. Four cases revealed discrepancies between the cytologic and histologic preparations. There was one false positive result, and one case was subconjunctival invasion of basal cell carcinoma of the eyelid. Impression and brush cytology are fast, cost-effective, reliable and noninvasive diagnostic tools for ocular surface squamous neoplasms. However, the brush technique has several advantages over impression cytology.

Surgical management of ocular surface squamous neoplasms: the experience from a cornea center.

To report the surgical outcomes of treatment for ocular surface squamous neoplasms. Retrospective review of squamous neoplasms of the ocular surface managed at a cornea center over a 15-year period. Surgical treatment was divided into two methods. The procedure was identical within each group. One group of patients was treated with simple excision of the lesion. The second group of patients was treated with excision followed by focal cryotherapy to the involved limbus and/or conjunctival margin. Follow-up is reported. A total of 28 lesions were reviewed. Included were 20 primary tumors and 8 recurrent tumors referred following initial treatment at other centers. Histopathologic diagnoses included 1 actinic keratosis, 7 dysplasias, 18 carcinomas in situ, and 2 invasive squamous cell carcinomas. The rate of recurrence for primary tumors was 28.5% with simple excision and 7.7% for excision combined with cryotherapy (p = 0.27). The rate of recurrence for recurrent tumors was higher: 16.6% for tumors treated with excision and cryotherapy and 50% (one in two) for lesions treated with simple excision (p = 0.46). Simple excision of ocular surface squamous neoplasms appears to result in a higher recurrence rate when compared to excision with adjunctive cryotherapy. Judicious cryotherapy to the involved limbus and conjunctival margins results in recurrence rates comparable with other, more extensive cryotherapy procedures. This technique of cryotherapy has very few adverse effects on the eye.