Differential diagnosis and treatment options for conjunctival tumors

The diagnostic classification of most conjunctival tumors is based on case history, inspection, and examination with the slit lamp microscope. Further imaging procedures are rarely indicated when malignant processes are not circumscribed. Clinical classification then also includes palpation and echographic examination of regional lymph nodes. Pigmented and nonpigmented melanocytic nevi are the most frequent conjunctival tumors. An important practical biomicroscopic cardinal symptom of the most frequent nevi is the presence of epithelial pseudocysts. Essential in practice is the histopathological confirmation of the clinical diagnosis, e.g., distinguishing between nonpigmented melanomas and sebaceous gland carcinomas with a pagetoid growth pattern or squamous cell carcinomas. Depending on the course and findings, the following therapeutic measures can be indicated: cryotherapy, chemotherapy, radiotherapy, modified enucleation, orbital exenteration, or a combination of different methods.     

Conjunctival tumors in children

PURPOSE OF REVIEW: Numerous conjunctival tumors can occur in children, originating from tissues of choristomatous, epithelial, melanocytic, vascular, fibrous, xanthomatous and lymphoid. Overall, 97% prove to be benign and only 3% are malignant. RECENT FINDINGS: The most common malignancies include conjunctival lymphoma and melanoma. In our experience, the most common conjunctival tumors in children include nevus (64%), dermolipoma (5%), lymphangioma (3%) and capillary hemangioma (3%). Conjunctival nevi can manifest as a darkly pigmented (65%), lightly pigmented (19%) and completely nonpigmented (16%) mass. Most nevi occurred at the nasal or temporal limbus, without involvement of the cornea. Occasionally, they are located in the caruncle, but rarely are nevi found in the fornix or tarsal conjunctival surface. Intralesional cysts are visible in 65% of nevi. Change in nevus color over time has been noted in 5% of cases and change in nevus size has been documented in 7%. Evolution of conjunctival nevus into malignant melanoma is extremely low (<1%). SUMMARY: Conjunctival nevus is the most common conjunctival tumor in children and fewer than 1% evolve into melanoma over time.     

Incidence of benign and malignant lesions of eyelid and conjunctival tumors

PURPOSE: To examine the incidence of benign and malignant eyelid lesions and conjunctival tumors. SUBJECTS AND METHODS: One-hundred-and twenty-eight cases (131 eyes) which were treated during the period from January 1990 to February 2004 were histopathologically diagnosed for eyelid or conjunctival tumors (87 cases of eyelid tumors and 41 cases of conjunctival tumors) in retrospective evaluations. The incidence of benign or malignant lesions, the pathological classification, age, sex, and clinical diagnostic accuracy were all investigated. RESULTS: Sixty-four (73%) of the tumors were found to be benign eyelid tumors. The common benign eyelid tumors were 14 nevocellular nevi, 9 seborrheic keratosis, 7 epidermoid cysts, and 6 papillomas. Twenty-four (27%) eyelid tumors were malignant. These included 9 basal cell carcinomas, 9 sebaceous gland carcinomas, 4 malignant lymphomas, and 2 metastatic tumors. Thirty-four (79%) conjunctival tumors were benign, and the common benign conjunctival tumors were 9 nevocellular nevi and 7 papillomas. Nine (21%) conjunctival tumors were malignant, comprising 7 malignant lymphomas and 2 squamous cell carcinomas. The mean ages of malignant eyelid and conjunctival tumor patients were significantly older than those of benign tumor patients. Clinical accuracy in predicting basal cell carcinoma and sebaceous gland carcinoma was 11.1% and 44.4%, respectively. CONCLUSIONS : Approximately 70 approximately 80% of all eyelid and conjunctival tumors are benign. Clinicians should suspect that the lesions are malignant when seeing elderly patients with eyelid or conjunctival tumors. Excised eyelid lesions should be submitted for histopathologic confirmation because there are some cases where clinical diagnosis does not match pathological diagnosis.     

S-100 protein in non-pigmented melanocytic and neuro-ectodermal tumors of the conjunctiva

Using an immunoperoxidase method, S-100 protein was localized in 51 nonpigmented or slightly pigmented nevi, eight malignant melanomas, three neurofibromas, and one neurilemmoma of the conjunctiva. Clinico-immunohistochemical correlations are presented. Cells of these neuroectodermal tumors contain S-100 protein. Epithelial invaginations arising from the conjunctival surface and lying between melanocytes are S-100 protein-negative. This facilitates the differential diagnosis of particularly amelanotic lesions of the conjunctiva. Immunohistochemical identification of the S-100 protein represents an improvement in current histochemical differential diagnosis of these tumors.     

Conjunctival balloon cell nevi--light- and electronmicroscopic findings in 2 patients

CASE REPORTS: Two 19-year-old patients presented with small nasal conjunctival tumors. Histologic examination revealed subepithelial tumors consisting of large cells with deeply basophilic, small, centrally-placed nuclei and abundant, slightly eosinophilic cytoplasm with microvesicles. Electron microscopy showed premelanosomes in some of the balloon cells. CONCLUSION: The balloon cell nevus is a rare variant of the conjunctival nevi. The characteristic intracellular microvesicles are probably degenerative remnants of premelanosomes.     

Conjunctival lesions in adults. A clinical and histopathologic review

A total of 2,455 conjunctival lesions in adults (over 15 years old) obtained during a 61-year period were reviewed and histopathologically classified as congenital, acquired epithelial, acquired subepithelial, pigmented, inflammatory/degenerative, and miscellaneous. The most common lesions in decreasing order of frequency were: pterygium, nevus, dysplasia, nonspecific nongranulomatous inflammation, and epithelial inclusion cyst. The most common conjunctival malignancy in adults was squamous cell carcinoma, followed by melanoma, and pagetoid change associated with sebaceous gland carcinoma. Squamous cell carcinomas arise from progressive stages of mild, moderate, and severe dysplasia. These tumors have a low malignant potential but may behave more aggressively in the spindle cell and mucoepidermoid variants. Melanomas arise de novo, from nevi or, most commonly, from acquired melanosis and have an associated 14-32% mortality rate by metastatic spread. Sebaceous carcinomas are often initially clinically misdiagnosed, involve the conjunctiva by pagetoid spread, and can have a low rate of metastasis and death if diagnosed early and excised with frozen-section monitoring of the surgical margins.     

Expression of intermediate filaments in conjunctival melanocytic lesions

BACKGROUND: To our knowledge there have been no studies on intermediate filament (IF) expression in conjunctival melanocytic tumors to date. Melanocytic lesions occurring at various body sites are known to express, in addition to the predominant IF protein vimentin, the epithelial-specific cytokeratins (CKs) and the neuronal IF peripherin. The present study was therefore carried out to assess the expression of IF proteins in conjunctival melanocytic lesions. METHODS: Paraffin-embedded material from 34 tumors - 16 conjunctival nevi, nine specimens of primary acquired melanosis (PAM; eight with and one without atypia), and nine conjunctival melanomas - was assessed after the application of a panel of antibodies directed against diverse IF proteins, including vimentin, CKs and peripherin. RESULTS: The most significant finding of this study was that all the tumors investigated expressed vimentin exclusively. While simple-epithelium CKs were found in epithelial cysts of nevi and in pseudoglandular portions adjacent to the melanoma, they were not identified in the tumor cells themselves. Similarly, peripherin and neurofilaments were not detected within any of the tumor cells. CONCLUSION: The IF expression pattern of conjunctival melanocytic lesions differs from that seen in melanocytic tumors of other body sites (including uveal melanomas), in that it includes neither CKs nor peripherin.     

26例结膜黑色素瘤的临床和病理学特点

目的 总结结膜黑色素瘤临床和病理学特点,以利于早期正确诊断和治疗.方法 回顾性系列病例研究.对天津市眼科医院从1985年5月至2007年6月间收治的26例结膜黑色素瘤的临床和病理学特点进行回顾性分析.病理学检查采用常规石蜡切片、HE染色,S-100蛋白和HMB-45免疫组织化学染色.结果 26例患者年龄30.0～83.0岁,平均53.4岁;均为单眼发病.26例中,11例起源于结膜原发性获得性黑变病恶变、8例起源于结膜色素痣或黑色素细胞瘤恶变、7例为原发性结膜黑色素瘤;14例肿瘤累及到睑结膜和球结膜、6例肿瘤位于球结膜、4例肿瘤位于睑结膜、2例肿瘤位于角膜缘;22例为上皮样细胞型黑色素瘤、4例为上皮样瘤细胞和梭形瘤细胞混合型.7例原发性黑色素瘤中有3例为无色素性黑色素瘤,瘤细胞对S-100蛋白和HMB45呈阳性表达.大多数肿瘤表面和邻近的结膜上皮内伴有瘤细胞侵犯.术后随访到14例,随访时间为1～18年.其中12例在肿瘤切除术后有1～3次肿瘤复发,3例有耳前淋巴结转移,1例有同侧耳前淋巴结和双侧颌下淋巴结转移,4例死于肿瘤全身扩散或肝转移.结论 结膜黑色素瘤主要是起源于结膜原发性获得性黑变病或色素痣恶变,大部分为上皮样细胞型黑色素瘤,伴有邻近结膜上皮内侵犯.术后复发比较常见,尤其肿瘤范围较大或伴有PAM者.     

Ultrasound biomicroscopy in pigmented conjunctival cystic nevi

PURPOSE: To report the use of ultrasound biomicroscopy in the clinical diagnosis and management of pigmented conjunctival cystic nevi. METHOD: Two patients, aged 11 and 18 years, with rapidly growing raised conjunctival melanocytic lesions suspected to be inflamed juvenile conjunctival nevus underwent ultrasound biomicroscopic and histopathologic examinations. RESULTS: Ultrasound biomicroscopic examination of the lesions revealed multiple areas of cystic tissue, which is compatible with pathologic finding of compound nevus with epithelial inclusion cysts formation. Furthermore, clear interface was found between the mass and the underlying sclera. CONCLUSION: Pigmented conjunctival nevi may obscure cysts under slit-lamp examination. Ultrasound biomicroscopy is a useful diagnostic adjunct to distinguish cysts in conjunctival lesions. Additionally, this technique may be helpful in delineating the extent of lesions prior to excision biopsy.     

The management of lid and conjunctival malignancies

Adnexal tumors are relatively rare in a general eye practice, and the most important component in their management is early recognition. The clear differentiation between simulating lesions and lid or conjunctival tumors can be difficult. Any recurrent lid inflammation, chronic lid ulcer, chronic unilateral keratoconjunctivitis, or a suspicious pigmented conjunctival lesion should be biopsied. The choice of treatment in lid and conjunctival tumors is partially dependent on the available surgical expertise. Lid tumors can be treated with either surgery (using frozen section control), radiation, or cryotherapy. Conjunctival tumors should first be biopsied, then treated with surgery or radiation. Exenteration is rarely indicated in the management of conjunctival tumors. A metastatic evaluation should precede possible exenteration, especially if this procedure is planned because of a recurrent or large conjunctival melanoma.     

Ocular histopathology of systemic mucopolysaccharidosis, type II-A (Hunter syndrome, severe)

A case of mucopolysaccharidosis, Type II-A (Hunter syndrome, severe) is described, with emphasis on ocular ultrastructural findings. Single membrane-bound structures containing fibrillogranular and, less commonly, multi-membranous material were found in conjunctival epithelium, pericytes and fibrocytes; corneal epithelium, keratocytes, and endothelium; trabecular endothelium; iris pigmented epithelium, smooth muscle, and fibrocytes; ciliary pigmented and nonpigmented epithelium and fibrocytes; retinal pigment epithelium and ganglion cells; optic nerve astrocytes and pericytes; and sclerocytes. The most striking accumulation was in the nonpigmented ciliary epithelium. These findings are compared with those seen in MPS II-B, and in other systemic mucopolysaccharidoses. The nature and distribution of inclusions are not specific to any one disorder, but help to signal the presence of one of the storage disorders. Distension of corneal keratocytes may play a role in the corneal clouding seen in some of these disorders. The importance of tissue examination, especially conjunctival biopsy, in the diagnosis of storage disorders and in assessment of future modes of therapy for the mucopolysaccharidoses is discussed.     

In vivo confocal microscopy of pigmented conjunctival tumors

PURPOSE: To analyze the appearance of conjunctival pigmented tumors as seen by in vivo confocal microscopy. METHODS: Twenty-eight pigmented conjunctival tumors including 6 nevi, 13 acquired melanoses, 7 conjunctival melanomas, and 2 extrascleral growths of uveal melanomas were examined by in vivo confocal microscopy using the Heidelberg Retina Tomograph (HRTII)/Rostock Cornea Modul (RCM). Confocal images were analyzed using predefined criteria by an observer masked to final histological diagnosis and a preliminary diagnosis was established. After excision, histology and immunohistochemistry using antibodies against S-100, Melan-A, HMB-45, Ki-67, CD3, and CD68 were performed in all specimens and compared with in vivo confocal images of the same lesions. RESULTS: Confocal microscopy images confirmed typical histopathological features of conjunctival pigmented tumors. Nest or diffuse collections of medium-sized uniform hyper- or hyperreflective cells in the stroma and stromal cysts lined with a multilayered epithelium were visible in 100% of conjunctival nevi. Small dendritic cells were typically observed in 100% of primary acquired melanoses (PAM) without atypia and in 2 out of 6 nevi. Large networks of hyperreflective dendritic cells were present in 100% of PAM with atypia. Whereas images of PAM without atypia and secondary complexion-associated melanosis showed hyperreflective granules confined to the basal epithelium in 67% of lesions, PAM with atypia presented with hyperreflective granules and patches throughout the epithelium in all cases. Malignant melanomas of the conjunctiva and extrascleral growths of uveal melanomas demonstrated large hyperreflective cells with prominent nuclei and nucleoli. In vivo confocal microscopy showed a sensitivity of 89% and a specificity of 100% to establish the correct diagnosis of conjunctival melanoma compared with histology. CONCLUSIONS: High correlations were found between in vivo confocal microscopy using near-infrared laser light and histology in the diagnosis of pigmented conjunctival lesions. In vivo confocal microscopy seems to be a valuable new tool in the differential diagnosis and follow-up of pigmented conjunctival tumors. It does not replace histology, but may assist in performing guided biopsy in tumors suspected clinically and/or with in vivo microscopy. In addition, in vivo confocal microscopy may support the clinical diagnosis of extrascleral involvement in uveal melanoma.     

葡萄膜与结膜色素性肿瘤核仁组成区银染定量研究

目的：评价银染核仁组成区(AgNORs)和计算机图像分析技术在结膜与葡萄膜色素性肿瘤良恶性鉴别诊断或冒后评估上的价值． 方法：应用AgNORs和计算机图像分析技术对44例葡萄膜恶性黑色素瘤、10例结膜色素痣及10例结膜恶性黑色索瘤进行检测。 结果：结膜恶性黑色素瘤较色素痣AeNORs面积显著增加(P<0.05)；葡萄膜恶性黑色索瘤AgNORs面积则按梭形细胞型、混合细胞型及上皮样细胞型顺序增加(P<0.05). 结论：AeNORs技术可能有助于结膜黑色素瘤良恶性的鉴别诊断，井可作为葡萄膜恶性黑色索瘤预后评价的参数之一。 （中华眼底病杂志，1995，11：181-184）     

Benign conjunctival melanocytic lesions. Clinicopathologic features

The common acquired conjunctival nevus usually undergoes progressive maturation and only exceptionally gives rise to conjunctival melanoma. Pure junctional nevi are rare except in childhood. Histologically, however, a junctional nevus may be indistinguishable from primary acquired melanosis (PAM) with atypia, a condition of middle-aged and elderly individuals that has a tendency to evolve into melanoma. Nevi in adolescents may attract a vigorous lymphocytic response and may cause clinical and histologic confusion with other entities, particularly a regressing nodule of melanoma that occurs predominantly in adults. Rarely, congenital conjunctival nevi are identified, sometimes in patients with adjacent congenital nevi of the eyelid. A variety of unusual nevi, including balloon-cell nevi, Spitz nevi, epithelioid cell nevi, dysplastic nevi, recurrent nevi, episcleral melanosis and the nevus of Ota, blue and cellular blue nevi, melanocytoma, and composite or mixed nevi all may be identified in the conjunctiva. Concepts of histogenesis as well as the clinical, light microscopic, and ultrastructural features of these and other benign pigmentary conditions of the conjunctiva are described.     

Eyelid tumors in children: a clinicopathologic study of a 10-year review in southern Taiwan

PURPOSE: To describe the clinical and histopathologic characteristics of eyelid tumors in children in southern Taiwan. METHODS: Patients younger than 17 years old with histologically confirmed eyelid tumors treated at Chang Gung Memorial Hospital (Kaohsiung) during 1991-2000 were subjected to a retrospective analysis. Patients with inflammation, granulation, hordeolum, chalazion and orbital or conjunctival extension were excluded. RESULTS: Totally, 78 patients (46 boys and 31 girls) with eyelid tumors were included. The 4 most common tumors, in order of frequency, were epidermal cysts (23.1%), dermoid cysts (17.9%), squamous cell papillomas (11.5%), and compound nevi (9%). Recurrence was noted in only 1 case (of a ductal cyst) after surgical excision during the 3-year follow-up period. CONCLUSIONS: Epithelial tumors and dermoid cysts are the most common eyelid tumors of children in southern Taiwan. Surgical excision produced good results. Malignant eyelid tumors are rare in children.     

777例原发性眼结膜肿瘤

目的:原发性眼结膜肿瘤的组织病理学分析。方法:常规石蜡包埋切片及HE染色,少数作PAS、网状纤维及免疫组化检查。结果:777例原发性结膜肿瘤中良性肿瘤(669例(86.1％),恶性肿瘤108例(13.9％)。良性肿瘤中色素痣247例(36.9％),其他依次为囊肿、皮样瘤及纤维脂肪瘤等。恶性肿瘤中鳞状细胞癌58例(53.7％),恶性黑色素瘤占第二位。结论:结膜良、恶性肿瘤某些生物学特性的差别,可作为鉴别诊断的参考。结膜的鳞状细胞癌中还有梭形细胞癌和粘液表皮样癌的病理类型及恶性黑色素瘤术后复发有多种病理因素。眼科学报 1995;11:211—215。