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[Immunohistochemical markers for cytoplasmic antigens in acquired melanosis, malignant melanomas, and nevi of the conjunctiva].

BACKGROUND: Benign and malignant melanocytic lesions of the conjunctiva are difficult to differentiate histologically. At present in the ophthalmologic literature there is not known a high specific and simply applicable histological feature (tumor marker) of differentiation to identify melanocytic lesions of the conjunctiva. METHODS: In this study 55 nevi, 15 primary acquired melanoses (stage Ia) and 54 melanomas of the conjunctiva were examined retrospectively immunhistochemically by antibodies vs. S-100 protein, and the melanoma-associated antigens HMB-45 and NKI/C3 using the labelled avidin-biotin method. 45 patients (25 female, 20 male) with malignant melanomas of the conjunctiva have been followed up clinically. RESULTS: S-100, HMB-45 and NKI/C3 are highly significant markers to identify malignant melanomas of the conjunctiva (sensitivity: S-100: 96.4%, HMB-45: 96.3%, NKI/C3: 98.1%), whereas markers in acquired melanoses (sensitivity: 93.3%, 78.6% and 92.9%), and nevi (sensitivity: 92.9% 40.7%, 98.2%) are not. Positive tumor markers do not correlate with local recurrences or metastasis. The localization of malignant melanomas and the lymphocytic infiltration are not prognostically significant. The only significant risk factor (p = 0.0485) predicting the development of recurrence or metastasis is tumor thickness > 1.5 mm. CONCLUSIONS: The tumor markers S-100, HMB-45 and NKI/C3 cannot differentiate reliably between benign and malignant melanocytic lesions of the conjunctiva, and positive tumor markers do not correlate with local recurrences or metastasis. The only significant risk factor (p = 0.0485) predicting the development of metastasis is tumor thickness (> 1.5 mm).

Adult↗

Eye manifestations in medullary carcinoma of the thyroid.

Multiple endocrine adenomatosis type III (MEA--III) in a 32-year-old white woman is reported. The initial manifestation, a thyroid nodule, was detected at the age of 4 years. The characteristic ocular manifestation of MEA--III are discussed.

Adrenal Gland Neoplasms↗

CD5 expression in a lymphoma of the mucosa-associated lymphoid tissue (MALT)-type as a marker for early dissemination and aggressive clinical behaviour.

Mucosa associated lymphoid tissue (MALT) developing in response to chronic infection or autoimmune stimuli has been recognized as a possible site of origin for a distinct type of B-cell lymphoma. While preferentially occurring in the stomach, MALT-type lymphomas can be found in virtually all organs. MALT-type lymphomas normally follow an indolent course, with a tendency to remain localized at their site of origin for a prolonged period of time. Histologically, MALT-type lymphomas are heterogeneous covering a cytological spectrum ranging from centrocyte-like cells to smaller lymphoid cells or monocytoid B-cells. Usually a small number of transformed blasts are also present. Immunohistochemically, the malignant cells express markers of B-cell lineage, but are distinct from follicular lymphomas (which express CD10), mantle cell lymphomas (expressing cyclin D1 and CD5) and small lymphocytic lymphoma, which express CD5 and CD23. In contrast to the usual phenotype CD20+CD10-CD5-Cyclin D1-, scattered reports in the literature have documented expression of CD5 in marginal zone B-cell lymphomas of MALT-type. However, these cases are rare, and aberrant CD5-expression has been thought to be a marker for early dissemination and aggressive behavior in some patients, while other reports have also found CD5 expression in localized indolent MALT-type lymphomas. We report a patient with a CD5+ MALT-type lymphoma following an aggressive clinical course without histological progression who relapsed only 18 months after local radiotherapy at the initial localizations (conjunctiva of the right upper eye lid and hypopharynx), and showed a rapid generalization to the contralateral conjunctiva, mediastinal lymph nodes and the esophagogastric junction. Our case lends further support to the notion that CD5+ MALT-lymphomas arising in the head-and-neck area and/or the ocular adnexa might be characterised by an aggressive clinical course.

Aged↗

Ocular melanoma.

Ocular melanomas are the most common intraocular malignancy in adults. The majority of ocular melanomas are choroidal melanomas. These tumors can be difficult to diagnose, especially when they are small. Documented growth of a lesion on serial examinations is the most important clinical feature favoring the diagnosis of a choroidal melanoma. Diagnostic studies including ultrasonography and angiography may be helpful in the diagnosis of these tumors. A number of treatment options are available for choroidal melanomas. These include photocoagulation, radiation therapy, local tumor resection, and enucleation.

Choroid Neoplasms↗

Caruncular malignant melanoma in a black patient.

An 84-year-old black woman had a right caruncular lesion that had progressively enlarged over the past 3 months. Surgical excision and cryotherapy were performed. A biopsy confirmed the diagnosis of caruncular malignant melanoma, a rare lesion which, to our knowledge, has not been previously reported in a black patient.

Aged↗

[Encephalocraniocutaneous lipomatosis. A non-hereditary mosaic phenotype].

Encephalocraniocutaneous lipomatosis is a distinct neurocutaneous syndrome characterized by an extensive fatty tissue nevus of the scalp, protuberances of the cranial bones, lipodermoid of the conjunctiva, multiple intercranial lipomas, and porencephaly. A further case of this multisystem birth defect is reported. The patchy arrangement of lesions that is usually unilateral suggests a mosaic phenotype. The clinical criteria to distinguish this disorder from other mosaic neurocutaneous phenotypes, such as Schimmelpenning syndrome, Proteus syndrome, or Delleman syndrome, are outlined. To explain the origin of this nonhereditary genodermatosis, the concept of a lethal autosomal mutation that survives in a mosaic state is proposed.

Brain Neoplasms↗

Sentinel lymph node biopsy for conjunctival melanoma.

OBJECTIVE: To investigate the feasibility and safety of preoperative lymphoscintigraphy and sentinel lymph node (SLN) biopsy for conjunctival melanoma. METHODS: A 49-year-old man with a biopsy-proven malignant melanoma of the conjunctiva (caruncle) underwent preoperative lymphoscintigraphy and SLN biopsy using a technique in which both isosulfan blue dye and technetium Tc 99 m sulfur colloid were injected in the subconjunctival space around the primary lesion. The conjunctival melanoma was excised just before identification and removal of the SLNs. The SLNs were excised along with concomitant dissection of their associated lymph node basins. The SLNs were evaluated histologically using serial sectioning and immunohistochemical staining with antisera against the S-100 protein and the melanoma antigen HMB-45. RESULTS: Three SLNs were identified in the left submandibular and the left upper and middle jugular lymph node basins during the preoperative lymphoscintigraphy. The same three SLNs were successfully identified in the operating room. The SLNs were histologically negative, and the immunohistochemical staining against S-100 and HMB-45 was also negative. We did not observe any immediate adverse effects on the globe or the periocular structures from lymphatic mapping and SLN biopsy. By 24 hours after injection of blue dye, only a faint trace of blue was visible on the ocular surface. CONCLUSIONS: Preoperative lymphoscintigraphy and SLN biopsy can be performed safely in patients with conjunctival melanoma. A larger study is planned to determine the sensitivity of this technique for the detection of occult regional nodal disease in patients with conjunctival melanoma.

Antigens, Neoplasm↗

Prognosis of conjunctival melanomas in relation to histopathological features.

Twenty-six patients (age 29-85 years) with primary malignant melanoma of the conjunctiva were analysed for usefulness of various histopathological and immunohistochemical features of the primary, recurrent and metastatic tumours in evaluating their prognosis. The mean follow-up time was 5.5 years, ranging from 8 months to 17 years. Eight patients developed metastases and seven have died. The mean time from diagnosis to death due to metastasis was 3.8 years (range 1-6 years). The site of the primary tumour seemed to be most closely correlated to high metastatic risk. Only two of the sixteen limbal melanomas metastasised, whereas two of the four bulbar, all three tarsal and the only diffuse primary tumour caused metastatic disease. Two of the metastasising primary tumours were less than 1.5 mm thick, but all exceeded 0.8 mm in thickness. The mitotic rate, the amount of inflammatory infiltrate, the cell type or the presence of adjacent intraepithelial involvement did not obviously correlate to treatment outcome. Furthermore, the expression of S-100 protein and neuron-specific enolase (NSE), both suggested to be prognostic indicators in cutaneous melanoma, did not correlate to the tendency of the conjunctival melanomas to recur or metastasise.

Adult↗

Mucosa-associated lymphoid tissue lymphoma with intraocular involvement.

PURPOSE: To report the clinicopathologic features of a patient with mucosa-associated lymphoid tissue (MALT) lymphoma of the conjunctiva and associated intraocular involvement. METHODS: This study is a retrospective clinicopathologic correlative case report summarizing the clinical, radiologic, and histopathologic findings of a patient with conjunctival MALT lymphoma and associated intraocular involvement. RESULTS: Ophthalmic examination and fluorescein angiography demonstrated progressive conjunctival infiltration bilaterally, marked uveal effusions in the left eye, and cellular white infiltrates of the choroid in the right eye. MRI of the orbit revealed a diffusely infiltrating intra- and extraocular lesion extending around the globe and optic nerve in the left eye without evidence of intracranial extension. Conjunctival biopsy showed low-grade tumor cells, consistent with the diagnosis of MALT lymphoma. The patient was successfully treated with external beam radiation with marked clinical improvement. CONCLUSION: Conjunctival MALT lymphomas, typically indolent and localized tumors, may extend into the orbit and invade local tissues such as the choroid with devastating consequences. A conjunctival biopsy can provide an easy diagnosis of this treatable entity.

Choroid Neoplasms↗

Differential immunoreactivity of melanocytic lesions of the conjunctiva.

AIMS: To evaluate the expression of S100NKI/C3 and HMB45 antigens in melanocytic lesions of the conjunctiva and the ability of HMB45 to aid assessment of neoplasia. METHODS AND RESULTS: Stored formalin-fixed specimens of conjunctival melanomas and primary acquired melanosis were considered as participants and conjunctival naevi and racial melanosis as controls. Ninety-seven conjunctival melanocytic lesions were analysed using formalin-fixed paraffin-embedded material. These included 20 melanomas arising in the context of primary acquired melanosis (PAM), 22 melanomas arising without evidence of pre-existing PAM, seven cases of PAM with atypia, nine cases of PAM with no atypia, 35 conjunctival naevi and four cases of racial melanosis. S100 and NKI/C3 were similarly expressed in all lesions, with at least one of these markers positive in 100% of the lesions examined. HMB45 was expressed in 72.7% of primary melanomas and 85% of melanomas in the context of PAM; 42.8% of PAM with atypia expressed HMB45 while it was expressed in 11.1% of PAM without atypia and 8.5% of naevi. Racial melanosis cases did not express HMB45. S100 and NKI/C3 were expressed to a similar extent in all groups. CONCLUSIONS: S100 and NKI/C3 are useful markers to assess the extent of melanocytic lesions in the conjunctiva. HMB45 immunoreactivity can act as a useful aid to histopathology for the distinction of benign from malignant conjunctival lesions, particularly in the context of primary acquired melanosis.

Antigens, Neoplasm↗

Seborrheic keratosis of conjunctiva simulating a malignant melanoma: an immunocytochemical study with impression cytology.

OBJECTIVE: Seborrheic keratosis on the conjunctiva appears to have never been reported in the literature. The authors report here a well-documented case of seborrheic keratosis of conjunctiva clinically simulating a malignant melanoma. DESIGN: Case report. METHODS: A 66-year-old man presented with a juxtalimbal pigmented tumor involving the temporal conjunctiva of his left eye. Because of the rapid enlargement of the mass within a period of 5 months, a clinical diagnosis of malignant melanoma was made. Cytopathologic examinations were performed by impression cytology before the patient underwent a wide en-block excision of the tumor. MAIN OUTCOME MEASURES: Cytologic features were studied by impression cytology with periodic acid-Schiff-Papanicolaou stain. Immunochemical characteristics of tumor cells were studied by immunochemical stain of cytokeratin and HMB-45. Tumor morphology was observed by histopathologic examination. RESULTS: Impression cytology disclosed basaloid cells intermixing with squamoid cells, and these cells demonstrated positive immunoreactivity to cytokeratin and no reactivity to HMB-45. Histopathologic examination of the tumor specimen established the diagnosis of seborrheic keratosis, and the results of immunohistochemical staining were consistent with those of the impression cytology with immunocytochemical staining. CONCLUSION: The authors describe the first case report of conjunctival seborrheic keratosis and present its immunocytochemical and immunohistochemical characteristics. Such a benign lesion can clinically mimic a malignant melanoma.

Aged↗

Conjunctival melanoma: risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients.

OBJECTIVE: To identify the risk factors of conjunctival malignant melanoma that predict local tumor recurrence, orbital exenteration, distant metastasis, and tumor-related mortality. DESIGN: The clinical parameters of the patient, tumor, and treatment were analyzed in a nonrandomized fashion for their relation to 4 main outcome measures using Cox proportional hazards regression models. PARTICIPANTS: One hundred fifty consecutive patients. MAIN OUTCOME MEASURES: Local tumor recurrence, orbital exenteration, distant metastasis, and death from conjunctival melanoma. RESULTS: The Kaplan-Meier estimates of local tumor recurrence was 26% at 5 years, 51% at 10 years, and 65% at 15 years. The mean number of recurrences per patient was 1 (median, 0 recurrences). There was no recurrence in 98 patients (65%), 1 recurrence in 28 patients (19%), 2 recurrences in 11 patients (7%), 3 recurrences in 5 patients (3%), and 4 or more recurrences in 8 patients (5%). Using multivariate analysis, the factors correlated with local tumor recurrence were melanoma location (not touching the limbus) (P =.01) and pathological tumor margins (lateral margin involved) (P =.02). Multivariate analysis for features correlated with ultimate exenteration included initial visual acuity (20/40 OU or worse) (P<. 001), melanoma color red (P =.01), and melanoma location (not touching the limbus) (P =.02). Tumor metastasis was present in 16% of patients at 5 years, 26% of patients at 10 years, and 32% of patients at 15 years. Metastasis was first located in the regional lymph nodes in 17 cases, the brain in 4 cases, the liver in 3 cases, the lung in 2 cases, and was disseminated in 1 case. The risks for metastases using multivariate analysis included pathological tumor margins (lateral margin involved) (P =.002) and melanoma location (not touching limbus) (P =.04). Tumor-related death occurred in 7% patients at 5 years' follow-up and 13% at 8 years' follow-up. The risk factors for death using multivariate analysis included initial symptoms (lump) (P =.004) and pathologic findings (de novo melanoma without primary acquired melanosis) (P =.05). The technique of initial surgery was shown to be an important factor in preventing eventual tumor recurrence (P =.07), metastasis (P =.03), and death (P =.006) in the univariate analysis, but did not reach significance in the multivariate analysis. CONCLUSIONS: Conjunctival malignant melanoma is a potentially deadly tumor. In the present study, metastasis was detected in 26% of patients, and death occurred in 13% of patients at 10 years. Extralimbal melanoma and tumor involvement of the surgical margins were especially poor prognostic factors. Meticulous surgical planning using wide microsurgical excisional biopsy working with the "no touch" technique and supplemental alcohol corneal epitheliectomy and conjunctival cryotherapy is advised. Arch Ophthalmol. 2000;118:1497-1507

Adolescent↗

An uncommon malignant neoplasm of the caruncle: report of a case of undifferentiated carcinoma.

The caruncle is an uncommon site for the occurrence of neoplasm despite its diverse histological composition of conjunctival, lacrimal, and skin tissues. The following case report describes a 66-year-old man who suffered from a primary undifferentiated carcinoma of the left caruncle. He remained well with no evidence of recurrence 24 months after a complete surgical excision. To our knowledge, this could represent the first case of undifferentiated carcinoma of the caruncle to be reported in the English literature. Early detection and complete excision for this type of lesion could lead to a satisfactory clinical outcome.

Aged↗

Multiple conjunctival metastases as the initial sign of metastatic uveal melanoma.

PURPOSE: To describe a 31-year-old patient who was initially examined with a uveal malignant melanoma metastatic to the ipsilateral conjunctiva. METHOD: Thirteen months after ruthenium 106 plaque therapy for a ciliochoroidal malignant melanoma, numerous pigmented conjunctival lesions first appeared. RESULTS: These lesions were excised and found to be metastases of melanoma to the superficial subepithelial conjunctival tissue, composed of epithelioid cells. CONCLUSION: The appearance of darkly pigmented conjunctival lesions in a patient known to harbor a uveal malignant melanoma, even though lacking any evidence of extrascleral extension or metastatic involvement, may indicate metastatic disease.

Adult↗

Unexpected histological findings in pterygium.

Pterygium is thought to be a common benign lesion of the corneo-conjunctival limbus. We report a case in which the pathological examination of an apparently trivial pterygium disclosed the presence of a conjunctival intraepithelial neoplasm in a 53-year-old white male who has been living in Kenya for 35 years. An atypical grayish area on the lesion convinced the surgeon to request the histological examination.

Carcinoma, Squamous Cell↗