Retrospective study of ocular surface squamous neoplasia

Background: Ocular surface squamous neoplasia (OSSN) encompasses the conditions of simple dysplasia to carcinoma in situ to invasive squamous cell carcinoma. It has a high rate of recurrence after treatment and the potential to metastasize. The present retrospective study was aimed at further defining the characteristics and clinical course of OSSN.
Methods: With ethical approval, the records of all major pathology laboratories in Queensland were surveyed. Two hundred and eighty-eight cases were identified: 155 dysplasia, 71 carcinomas in situ and 62 invasive squamous cell carcinoma. The records were analysed and an attempt was made to contact and re-examine the patients.
Results: Ocular surface squamous neoplasia occurs mainly in males (78.5%) with a mean age of 60.1 years (range 20–88 years). They present as irritation (40.1%) and are located usually at the limbus (87.8%). The majority of OSSN are treated by simple excision (87.5%), after which there is a high rate of recurrence (23.3%). The main predictors for recurrence include histological grade of the lesion, corneal location and larger size (> 2 mm).
Conclusions: Management of OSSN requires adequate excision and careful follow up to monitor any recurrence. As with other ultraviolet light-related conditions, preventative measures must remain the key to disease control.     

眼表鳞状细胞瘤局部药物治疗进展

眼表鳞状细胞瘤（ocular surface squamous neoplasia,OSSN）是眼科常见的眼表肿瘤,眼局部药物治疗具有非侵入性、创伤小的优点,有逐渐取代手术切除成为其首选治疗方式的趋势。目前局部药物除采用抗代谢、抗肿瘤、免疫调节作用的药物（丝裂霉素C、5-氟尿嘧啶、干扰素 α2b、维甲酸等）外,一些抗肿瘤血管及病因治疗的药物（抗血管内皮生长因子类药物、西多福韦等）也被用于OSSN临床治疗研究中。（国际眼科纵览,2020, 45： 380-386）     

眼表鳞状上皮瘤研究进展

眼表鳞状上皮瘤(OSSN)是临床上少见的眼表肿瘤,由于其发病率低,且易与翼状胬肉等混淆,给诊断造成困难。近年来,各种诊断技术的提高,以及干扰素(interferon,IFN)广泛应用于OSSN治疗,大幅度降低复发率,OSSN诊断治疗手段趋于多样化。了解当前OSSN发病原因以及治疗方式,可以更好地指导OSSN研究。     

Ocular surface squamous neoplasia

Ocular surface squamous neoplasia presents as a spectrum from simple dysplasia to carcinoma in situ to invasive squamous cell carcinoma involving the conjunctiva as well as the cornea. It is a distinct clinical entity, although it has been known by a variety of different names thorughout the literature. Most commonly it arises in the limbal region, occurring particularly in elderly males who have lived in geographic areas exposed to high levels of ultraviolet-B radiation. Symptoms range from none to severe pain and visual loss. The development of preoperative diagnostic techniques, such as impression cytology, are of value in clinical decision making and follow-up management. Simple excision with adequate margins is currently the best established form of treatment despite trials of other modalities. The course of this disease may be evanescent, but is more frequently slowly progressive and may require exenteration and occasionally may lead to death.     

Amniotic membrane transplantation with topical interferon alfa-2b after excision of ocular surface squamous neoplasia

To evaluate the outcome of amniotic membrane transplantation (AMT) after tumor excision followed by topical interferon alfa-2b (IFNα2b) drops for primary ocular surface squamous neoplasia (OSSN). Twelve eyes of 12 patients with a mean age of 66±10y were included. The average follow-up was 23±10mo. All 12 patients had limbal involvement. Smooth ocular surface and transparent cornea were achieved in all cases. No sign of inflammation, neovascularization, symblepharon or recurrence was noted at the last follow-up. We conclude that AMT with topical IFNα2b drops restores a healthy ocular surface in OSSN without recurrence.     

Pseudoepitheliomatous hyperplasia mimicking ocular surface squamous neoplasia following cultivated limbal epithelium transplantation

A 12-year-old girl with total limbal stem cell deficiency in the right eye following chemical burns underwent autologous cultivated limbal epithelium transplantation from the healthy left eye. Postoperatively at 6 weeks a mass at the limbus was noted, which increased in size and involved infero-nasal limbus extending over 5 mm on bulbar conjunctiva. It was a gelatinous, placoid freely movable mass with irregular surface, multiple intralesional cysts without feeder vessels or intrinsic vascularization and stained brilliantly with rose bengal. Histopathology following excision biopsy showed hyperplastic epithelium with stratified columnar cells and goblet cells. At the last follow-up, 6 months following cultivated limbal epithelium transplantation the ocular surface was stable without any recurrence of the lesion. We herein report a rare complication of epithelial hyperplasia presenting as leukoplakia following cultivated limbal epithelium transplantation mimicking ocular surface squamous neoplasia.     

Factors affecting recurrence after surgical treatment in cases with ocular surface squamous neoplasia

AIM: To evaluate the risk factors leading to recurrence in patients with ocular surface squamous neoplasia (OSSN) METHODS: The records of 112 patients with OSSN who underwent treatment and follow-up between February 1999 and August 2018 were reviewed retrospectively. RESULTS: Totally 67 patients (59.8%) were male and 45 patients (40.2%) were female. The mean age at presentation was 63.7y (range 22-87y). Partial lamellar scleroconjunctivectomy (PLSC) was performed in 105 (93.7%) cases and enucleation was performed in 7 (6.3%) cases due to bulbus invasion as the first step treatment. Treatments used in addition to PLSC included cryotherapy in 78 eyes (74.3%), alcohol epitheliectomy in 57 eyes (54.3%) for presence of corneal involvement, and amniotic membrane transplantation in 17 eyes (16.2%) for ocular surface reconstruction. Topical mitomycin C was used in 10 patients (9.5%) and strontium-90 (Str-90) treatment in 4 (3.8%) patients because surgical margins were tumor positive at the histopathological examination. Postoperative histopathologic diagnoses were squamous cell carcinoma (52 cases), carcinoma in situ (44 cases), moderate conjunctival intraepithelial neoplasia (11 cases), and mild conjunctiva intraepithelial neoplasia (5 cases). At a mean follow-up of 20.1mo, tumor recurrence was observed in 21 (18.8%) cases. The rate of recurrence was found to be lower in cases that underwent supplemental cryotherapy compared to those that did not (P<0.001). There was no metastasis in any case. CONCLUSION: In our series, the recurrence rate is 18.8% and overall globe salvage rate is 90.2% for OSSN at relatively short-term follow-up.     

The clinical value of in vivo confocal microscopy for diagnosis of ocular surface squamous neoplasia

Purpose

To determine the reliability and efficiency of in vivo confocal microscopy for the diagnosis of ocular surface squamous neoplasia (OSSN).

Methods

A case series with five consecutive cases of OSSN were investigated retrospectively, of which the characteristics and subspecial types had been estimated by in vivo confocal microscopy before surgery. The structure and cellular features of OSSN were analyzed with other examinations, such as anterior-segment optical coherence tomography (AS-OCT), and confirmed by histopathological biopsy.

Results

The tumors revealed red gelatinous surfaces with vascular dilatation on the ocular surface of the conjunctival and corneal epithelium in anterior segment photography. Involvement of only corneal epithelium was observed by AS-OCT in three cases, whereas the Bowman''s layer and anterior stroma were also invaded in the other two cases. In vivo confocal microscopy showed cellular anisocytosis and enlarged nuclei with high nuclear to cytoplasmic ratio in three cases diagnosed as conjunctival intraepithelial neoplasia; moreover, nests were partially formed by isolated keratinized, binucleated, and actively mitotic dysmorphic epithelial cells in the other two cases diagnosed as carcinoma in situ and ocular surface squamous carcinoma (OSSC). The characteristics assessed from histopathological biopsy were similar to that revealed by in vivo confocal microscopy in all five cases.

Conclusion

In vivo confocal microscopy analysis of cytological characteristics of OSSN is a safe, relatively noninvasive, and effective diagnostic tool in detecting characteristics of OSSN before surgical resection. Although in vivo confocal microscopy cannot replace excisional biopsy for definitive diagnosis, it can be valuable for initial diagnosis and management of patients with OSSN.     

光相干断层扫描技术在眼表鳞状上皮瘤诊疗中的应用及展望

眼前节光相干断层扫描技术(AS-OCT)作为一种无创性检查手段,具有检测肿瘤性上皮病变的巨大潜力。依据AS-OCT上的特征性表现,可在多种眼表疾病中检测出眼表鳞状上皮瘤(OSSN)的存在,其诊断效果堪比病理组织活检。随着技术的发展,AS-OCT成像模式已从时域OCT发展到具有更高外显率和分辨率的频域OCT,其呈现的高质...     

眼表鳞状细胞瘤的药物治疗现状

眼表鳞状细胞瘤(OSSN)是眼表最常见的无色素肿瘤,手术切除是该类疾病最根本的治疗方式。"零接触"手术方式辅助冷冻疗法有助于避免肿瘤向周围组织扩散,但对于较大、累及视轴、复发性、多灶性或弥漫性病变,手术可能无法完全清除病灶,达不到理想的治疗效果,并且存在术后角膜缘干细胞缺乏、瘢痕形成和睑球粘连的风险。局部药物治疗由于药...     

Ocular surface squamous neoplasia as the first apparent manifestation of HIV infection in Malawi

Purpose:  To evaluate the prevalence of undiagnosed and asymptomatic HIV infection in patients with ocular surface squamous neoplasia (OSSN) in an urban patient population in Malawi.
Methods:  A consecutive series of patients presenting with OSSN was evaluated in an African academic centre. A detailed history and physical examination in 53 consecutive patients with conjunctival squamous cell carcinoma and conjunctival intraepithelial neoplasia were performed. Thirty-eight (72%) patients agreed to undergo serological HIV testing.
Results:  Seventy-nine per cent (30 of 38) patients were HIV positive. None of the patients had previous HIV testing or was aware of having symptoms of HIV. Seventy per cent ( n  = 21) of the HIV-positive patients had no other symptoms suggestive of HIV infection or any other disease. Patients were far more likely to refuse HIV testing if they were married and male.
Conclusions:  The conjunctival tumour may be the primary and only apparent manifestation of HIV in patients presenting with OSSN in Sub-Saharan Africa.     

Management of ocular surface squamous neoplasia extending up to a filtering trabeculectomy bleb

A 73-year-old-gentleman was referred for ocular surface squamous neoplasia (OSSN) in his right eye (RE). He had history of combined cataract with trabeculectomy in RE and was maintaining his intraocular pressure (IOP). He showed a corneoscleral lesion measuring 11 × 8 mm in nasal quadrant wherein, the superior edge of the lesion was extending up to the filtering bleb. After ruling out intraocular invasion or regional spread, he underwent complete tumor excision with “no touch” technique along with cryotherapy and surface reconstruction and a perilesional injection of Interferon α2B. At 6-month visit, he shows no locoregional recurrence and has controlled IOP.     

共聚焦显微镜在活体角膜上皮肿瘤鉴别诊断中的应用

目的 通过活体共聚焦显微镜在角膜上皮肿瘤诊断中的应用,分析、鉴别角膜上皮肿瘤性质.方法 7例角膜上皮肿瘤患者术前均行常规眼部裂隙灯检查、眼前节OCT和活体共聚焦显微镜检查.所有患者均实施角膜肿瘤切除术,术后行肿瘤组织病理学检查,与术前共聚焦显微镜结果比较.结果 7例角膜上皮肿瘤均侵犯透明角膜、角膜缘和球结膜,突起于眼球表面,形状似桑葚,血管丰富.在眼前节OCT检查中5例角膜肿瘤显示密度均匀,与角膜组织之间界限清晰,浅层基质中未见肿瘤密度影;另外2例角膜肿瘤显示,密度不均,与角膜组织界限不清,而且侵犯前弹力层和浅层角膜基质.在活体共聚焦显微镜中7例均显示角膜上皮细胞非典型增生,其中2例非典型增生明显,侵犯前弹力层,在角膜上皮层和浅基质层内形成“癌巢”,5例诊断为角、结膜乳头状瘤,2例诊断为角膜鳞状上皮细胞癌,与术后组织病理学诊断结果一致.结论 活体共聚焦显微镜检查对角膜上皮肿瘤术前诊断肿瘤性质提供重要依据.     

Role of high resolution optical coherence tomography in diagnosing ocular surface squamous neoplasia with coexisting ocular surface diseases

Purpose

Coexistence of an ocular surface disease can mask the typical features of ocular surface squamous neoplasia (OSSN). The purpose of this study was to evaluate high resolution optical coherence tomography (HR-OCT) as an adjunct in the detection and differentiation of OSSN within coexisting ocular surface pathologies.

Primary treatment of ocular surface squamous neoplasia with topical interferon alpha-2b: Comparative analysis of outcomes based on original tumor configuration

Purpose:The aim of this study was to evaluate tumor control of OSSN with topical IFNα2b alone based on tumor configuration (flat versus (vs.) dome-shaped).Methods:Retrospective, nonrandomized, interventional cohort study on 64 consecutive tumors in 63 patients with OSSN treated with topical IFNα2b. Topical IFNα2b (1 million international units/cc) was compounded and provided by the Thomas Jefferson University Hospital Pharmacy to be refrigerated and applied 4 times daily until biomicroscopic evidence of tumor resolution was observed.Results:The tumor configuration was flat (n = 15, 23%) or dome-shaped (n = 49, 77%). A comparison (flat vs. dome-shaped) revealed dome-shaped with older mean patient age at presentation (62 vs. 70 years, P = 0.04), greater patient history of smoking (13% vs. 42%, P = 0.04), greater corneal involvement (7% vs. 82%, P < 0.001), larger mean basal diameter (5.5 vs. 12.4 mm, P = 0.001) and mean thickness (1.9 vs. 4.3, P = 0.002), and longer mean duration IFNα2b therapy (3.7 vs. 6.3 months, P = 0.002). There was no difference in mean follow-up time (22.2 vs 23.1 months) or time to complete response (5.0 vs. 6.1 months). There was no difference in achievement of complete tumor control with IFNα2b alone (93% vs. 96%). There were no cases with metastasis or death.Conclusion:Topical IFNα2b alone shows excellent overall tumor control of 95% with no difference in efficacy based on tumor configuration.     

Tumors of the ocular surface: A review

Tumors of the Ocular Surface clinically manifest with a very wide spectrum and include several forms of epithelial, stromal, caruncular, and secondary tumors. As a group, these tumors are seen commonly in the clinical practice of a comprehensive ophthalmologist, cornea specialist, and an ocular oncologist. This review is aimed to discuss the common tumors of the ocular surface and emphasize on their clinical diagnosis and appropriate management.     

眼球表面鳞状细胞性肿物的临床病理学分析

目的:提高对眼球表面鳞状细胞性肿物的诊断和治疗水平。方法:对天津眼科医院1978～1997年收治的180例眼球表面鳞状细胞性肿物进行临床和病理学分析。结果:本组病变可分为三大类:1良性病变73例(40.4%),包括鳞状细胞增生、乳头状瘤和假上皮瘤样增生;2交界性病变42例(23.3%),主要是非典型增生;3恶性病变65例(35.9%),包括原位癌、鳞状细胞癌和粘液表皮样癌。本组病变好发于角膜缘部位(118例),男性多见(145例),通常为单眼发病,多数发病时间为半年～1年内。手术后复发主要与肿物切除不彻底有关。结论:对眼球表面鳞状细胞性肿物的术前正确诊断、手术设计和手术边缘的病理学检查是非常重要。     

眼球表面鳞状细胞肿瘤107例临床分析

为探讨眼球表面鳞状细胞肿瘤（Ｏｃｕｌａｒｓｕｒｆａｃｅｓｑｕａｍｏｕｓｎｅｏｐｌａｓｉａ，ＯＳＳＮ）的分型及临床特点。对赞比亚恩多拉中心医院眼科门诊１０７例眼球表面鳞状细胞肿瘤进行回顾性分析。结果：在１０７例眼球表面鳞状细胞肿瘤中，结角膜上皮内肿瘤（Ｃｏｎｊｕｎｃｔｉｖａｌａｎｄｃｏｒｎｅａｌｉｎｔｒａｅｐｉｔｈｅｌｉａｌｎｅｏｐｌａｓｉａ，ＣＩＮ）５３例，鳞状细胞癌（Ｓｑｕａｍｏｕｓｃｅｌｃａｒｃｉｎｏｍａ，ＳＣＣ）５４例，在ＣＩＮ中，非典型增生（Ｄｙｓｐｌａｓｉａ）４４例，原位癌（Ｃａｒｃｉｎｏｍａｉｎｓｉｔｕ）９例，在ＳＣＣ中，４例侵犯眼球或眼眶。患者多为年轻人，年龄最小１４岁，最大６２岁，平均年龄ＣＩＮ为３４岁，ＳＣＣ为３６岁。女性略多于男性，病变多为早期，较少侵犯眼内。结论：该肿瘤为赞比亚常见眼病，年轻患者多，紫外线照射和感染可能是其主要发病因素；早期诊断、早期手术是治疗本病的关键