[Case of corneally displaced malignant conjunctival melanoma].

BACKGROUND: We studied the clinicopathologic characteristics in a patient with malignant conjunctival melanoma associated with corneal invasion. CASE: A 62-year-old man had a small melanocytic lesion of the inferior palpebral conjunctiva. Previously he had undergone excisional biopsy and was diagnosed as having melanocytic hyperplasia without cytological atypia at an other hospital. He developed recurrence and was referred to us. The pigmentary lesion was observed in the entire inferior palpebral conjunctiva. Biomicroscopic examination revealed that there was a granular pigment lesion in the cornea. The patient was diagnosed as having conjunctival melanoma with corneal invasion and treated with orbital exenteration and chemotherapy in our hospital. Clinicopathologic tests revealed malignant melanoma cells invading through the bulbar conjunctiva and into the cornea. Ultrastructural study by electron microscopy of the pigmented tumor cells in the cornea showed several lobations of the nuclei, a large active-appearing nucleolus, and an aberrant granular melanosomal morphology. CONCLUSIONS: The infiltration of palpebral malignant conjunctival melanoma was limited to the epidermis of the cornea.

Malignant melanoma of the palpebral conjunctiva in a captive fallow deer.

A case of malignant melanoma in the conjunctiva of the eyelid of a captive 13-yr-old female fallow deer (Dama dama) was studied. The black tumor that protruded to the palpebral conjunctiva of the right lower eyelid consisted of an infiltrative growth of melanin-containing neoplastic cells with marked cytological atypia. The tumor involved the conjunctiva of the right lower eyelid and infiltrated to the conjunctival epithelial layer, but did not reach the palpebral skin. Numerous mitotic figures and lymphatic invasions were observed. This is a very rare case of a malignant melanoma arising from the palpebral conjunctiva in a wild ruminant.

[Pathological and ultrastructural changes in conjunctival malignant melanoma treated by cryotherapy].

The liquid nitrogen cryotherapy was used to treat conjunctival malignant melanoma. Light and transmission electron microscopic examinations were carried out before, during and after the treatment. It was discovered that the tumor cells died within a few minutes after the cryoapplication. Under transmission electron microscope, marked necrosis of tumor cells was seen 10-14 days after the treatment and a large amount of collagenous fibers and fibroblast hyperplasia were seen in the tumor in 3-4 weeks following the application, while the tumor cells were seldom found. Under light microscope, as significant necrosis of the malignant melanoma occurred, the surface conjunctival epithelium gradually grew and covered the defect of the conjunctiva, showing that the malignant melanoma cells are much more sensitive to the cryoapplication than the normal conjunctival epithelial cells.

Nucleolar organizer regions in determining malignancy of pigmented conjunctival lesions.

We assessed the usefulness of silver staining of nucleolar organizer regions in the diagnosis of pigmented conjunctival tumors. Fifty-one biopsy specimens were silver stained to identify the nucleolar organizer regions. Nineteen nevi without atypia, three nevi with atypia, eight primary acquired melanosis lesions, and 14 melanomas were studied. In each specimen, silver staining of the nucleolar organizer regions was counted in 100 cells to yield an average of the silver staining of the nucleolar organizer region count. The mean silver staining of the nucleolar organizer region counts per cell was correlated with the degree of malignancy of pigmented conjunctival lesions as follows: nevi, 3.0; primary acquired melanosis, 3.2; nevi with atypia, 3.9; primary acquired melanosis with atypia, 5.0; and melanoma, 5.7 (Spearman correlation [rS] = .83, P = .0001; analysis of variance [ANOVA] F test = 20.9, P = .0001). A cutoff value of 4.0 (mean silver staining of nucleolar organizer regions per cell) will differentiate melanoma and primary acquired melanosis with atypia from other lesions (sensitivity, 100%; specificity, 96%). The silver staining of nucleolar organizer regions is a useful adjunct in determining the malignancy of pigmented conjunctival tumors.

Significance, specificity, and ultrastructural localization of HMB-45 antigen in pigmented ocular tumors.

PURPOSE: To evaluate the expression of the monoclonal HMB-45 antibody in melanocytic and nonmelanocytic ocular tumors and seek "activated" cellular subpopulations in an attempt to distinguish between benign and malignant melanocytes, to compare HMB-45 and S100 activity, and to determine the specificity of this tumor marker for melanocytic ocular lesions. METHODS: Immunohistologic investigations were performed with paraffin-embedded tissue of 10 acquired conjunctival melanoses, 19 conjunctival nevi, 34 conjunctival melanomas, 69 uveal melanomas, 20 basal cell carcinomas of the lid, 20 cystic dermoids, 15 hemangiomas of the lid, 20 conjunctival papillomas, 20 squamous cell carcinomas, 20 pterygia, 11 sebaceous gland carcinomas, 10 retinoblastomas, and 5 choroidal metastatic carcinomas. The avidin-biotin peroxidase technique and monoclonal HMB-45 antibody were used. The distribution of S100 protein was studied in the melanocytic tumors for comparison. To localize the HMB-45 antigen, lowicryl-embedded tissue of uveal melanomas was investigated immunoelectron microscopically. RESULTS: More than 95% of the conjunctival and choroidal melanomas expressed the HMB-45 antigen, while S100 was found in all melanomas of the conjunctiva and in 91% of the uveal melanomas. In benign melanocytic lesions of the conjunctiva (nevi and melanocytes), especially the intraepithelial and junctional components stained with HMB-45, and at the site of tumor invasion, infiltrating cells showed increased HMB-45 reactivity. On the whole, HMB-45 antigen was less evenly distributed in the melanocytic tumors investigated than S100 antigen. All nonmelanocytic ocular tumors revealed no HMB-45 expression. Retinal pigment epithelium and tumor-free choroid were negative for HMB-45. The HMB-45 antigen was immunoelectron microscopically found in melanosomes at stages II and III. CONCLUSION: HMB-45 immunohistology helps in distinguishing melanocytic from nonmelanocytic ocular tumors and often clarifies the front of tumor invasion. The stronger HMB-45 reactivity probably reflects melanocytic activation, but a sharp line between benign and malignant melanocytes cannot be drawn.

Gastric adenocarcinoma presenting as an eyelid and conjunctival mass.

A 50-year-old white man complained of "inflammation" of his right eyelid since January 1989. In June 1990, he had undergone a gastrectomy for an adenocarcinoma of the stomach. In August 1990, his right eye showed a painless, firm infiltration of the upper and lower lid, ulceration and loss of eyelashes of the upper lid and a reddish, subepithelial thickening of the medial bulbar conjunctiva. Biopsies of the right upper lid and nasal bulbar conjunctiva disclosed a metastatic, poorly differentiated adenocarcinoma of the stomach (signet ring cell carcinoma) both in the lid and conjunctival biopsies. Carcinoembryonic antigen (CEA) was detected in the tumor cells. Electron microscopic examination revealed tumor cells with signs of secretory activity. Although metastases to the eyelids and conjunctiva are rare, they may precede the clinical manifestation of the primary tumor for months or even years. In patients with chronic, recalcitrant lesions of eyelids or conjunctiva, especially if accompanied by loss of eyelashes, a primary or secondary malignancy should be excluded by early biopsies and histopathological examination.

Krause's end-bulb microtumor of the conjunctiva: optic and ultrastructural description of a case.

Ultrastructural examination of a conjunctival biopsy of a 90-year-old woman with a history of chronic lymphatic leukemia showed numerous densely packed structures located below the epithelial conjunctival layer. They were composed of concentrical flattened lamellae arranged around one or several clear cores containing a large number of mitochondria. The plasma membranes of the lamellae displayed large numbers of pinocytotic vesicles and resembled perineurial cell processes. The central areas were thought to be axons. Because of their conjunctional location and morphological features. The structures were categorized as nerve endings of the Krause's end-bulb type. The aberrant and profuse growth of these structures led to the diagnosis of Krause's end-bulb microtumor of the conjunctiva. We compare our findings with mucosal neuromas, paraneoplastic lesions and age-related alterations are discussed, although they differ morphologically from Krause's end-bulb microtumor.

Leiomyosarcoma of the conjunctiva.

The clinical, light microscopic, immunohistologic, and ultrastructural findings of a leiomyosarcoma of the conjunctiva are presented. This tumor was diagnosed after a 26-year history and is the first to be adequately documented as having arisen in the conjunctiva.

Spindle cell carcinoma of the conjunctiva. An immunohistochemical and ultrastructural study of six cases.

Six cases of conjunctival spindle cell carcinoma, a rare variant of squamous cell carcinoma, were studied. The median age of the three men and three women was 63.5 years. The tumors appeared as a single nodule in some patients or diffusely involved the conjunctiva in others. Two of the four individuals with intraocular extension presented with phthisis bulbi. Polyclonal antikeratin antibody was helpful and gave the most consistent results when compared with monoclonal antikeratin antibodies, AE1/3 and PKK1. The electron microscopic study of four lesions also established the epithelial nature of the tumor cells. Intracytoplasmic tonofilaments and a few desmosomes were present. Histopathologically, this variant of squamous cell carcinoma is difficult to distinguish from other spindle cell tumors, and this study demonstrates the value of immunohistochemistry and electron microscopy in supporting the correct diagnosis.

Dacryoadenoma. A unique tumor of the conjunctival epithelium.

For 15 years, a 48-year-old woman had been aware of a pinkish translucent inferior epibulbar mass toward the fornix that was stationary in size. Light microscopic evaluation of the excised specimen showed that it was a gland-forming benign tumor. It originated from the surface epithelium by the downward invagination of tubular formations that underwent secondary and tertiary ramifications. The surface epithelium overlying the mass was not normal conjunctival squamous epithelium, but it was a modification in the form of a superficial layer of columnar to cuboidal cells surmounting several nuclei similar to the cells lining the subepithelial lumen-forming units. Electron microscopy showed that both the surface and tumor epithelium contained apical lacrimal-type zymogen granules and basilar whorls of rough-surfaced endoplasmic reticulum. Scattered myoepithelial cells were associated with the acinar-type epithelium of the tumor, and there were goblet cells intermixed. Neither light nor electron microscopy disclosed the presence of true ducts. The authors conclude that the lesion was a benign proliferation of lacrimal secretory-type cells and suggest the term "dacryoadenoma" for this previously undescribed entity.

Spindle cell carcinoma of cornea and conjunctiva with pseudosarcomatous metaplasia. Light microscopic, electron microscopic and immunohistochemical findings in 2 patients.

We studied the electron microscopic and immunohistochemical findings in two elderly patients with spindle cell carcinoma of the cornea and conjunctiva. By light microscopy, correct diagnosis was made by finding the transition between the pleomorphic spindle shaped tumor cells and the overlying squamous epithelium. Ultrastructural findings indicated that squamous cell origin included tonofilament-associated desmosomes and keratohyaline granules in the tumor cells. Positive immunohistochemical staining with antikeratin antibodies provided further evidence to prove the origin of spindle cell carcinoma. Follow-up of the two patients showed the malignant tumor to be quite aggressive in terms of intraocular invasion in the first patient and local recurrence in the second.

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.

Clinicopathologic characteristics of premalignant and malignant melanocytic lesions of the conjunctiva.

Primary acquired melanosis (PAM), a disease that affects mostly middle-aged white patients, is predominantly a proliferative condition of the melanocytes that normally populate the conjunctival epithelium. Primary acquired melanosis without atypia (low risk for the development of melanoma) is typically created by increased numbers of melanocytes restricted to the basilar region of the epithelium without nuclear hyperchromasia or prominence of the nucleoli. Primary acquired melanosis with atypia, a formal precursor of melanoma, is characterized by the proliferation of small polyhedral cells, spindle cells, large dendritiform melanocytes, or epithelioid cells that may: remain restricted to the basilar region (basilar nests); form nests at all levels of the epithelium; spread individually to all levels of the epithelium (pagetoid extension); or proliferate in a sheet-like fashion approximating a melanoma in situ. Lesions composed of epithelioid cells or exhibiting intraepithelial pagetoid extension have, respectively, a 75 or 90% chance of eventuating in invasive melanoma. Primary acquired melanosis in an adult should not be confused with "a junctional nevus," which is almost always restricted to childhood. Invasive melanomas measuring less than 0.8 mm in thickness tend not to be associated with metastases; the tumor cells may be small polyhedral (in which case confusion with a compound nevus often arises), epithelioid, spindled, or ballooned. Nodules composed of spindle cells in part or in toto tend to have less metastatic potential at a given thickness measurement than comparable nodules composed of epithelioid or polyhedral cells. The clinical features, electron microscopic findings, and biologic principles underwriting clinical management are also presented.

Infantile subconjunctival and anterior orbital fibrous histiocytoma. Ultrastructural and immunohistochemical studies.

A fleshy, polypoidal and partially lobulated lesion that protruded between the eyelids from the medial caruncular region and that infiltrated the contiguous anterior orbital tissues developed over 1 month in a 9-month-old infant. The microscopic features of the tumor included a plump spindle cell population, more polygonal cells, early xanthoma cell transformation, infiltrating lymphocytes and eosinophils, and multinucleated giant cells, the last not exhibiting classic Touton characteristics. The histopathologic differential diagnosis ranged among fibrous histiocytoma, juvenile xanthogranuloma, and eosinophilic granuloma (histiocytosis-X). Results of electron microscopy disclosed abundant rough-surfaced endoplasmic reticulum, a paucity of lysosomes, and no Langerhans' (Birbeck) granules. Immunohistochemistry corroborated the fibrohistiocytic nature of the tumor, because histochemical stains for the enzymes alpha-1-antichymotrypsin and lysozyme, and monoclonal or polyclonal antibodies against common leukocytic antigen and S-100 protein, were negative--whereas they would have been expected to be positive in various combinations in the different histiocytic proliferations. Vimentin was identified in the tumor cells; this is an intermediate cytoplasmic filament almost always present in mesenchymal proliferations. The distinctions between fibrous histiocytomas of stromal cell origin and true histiocytic proliferations of bone marrow cell provenance are explored.

Recurrent conjunctival melanoma with neuroidal spindle cell features.

A 66-year-old white woman had had a 20-year history of flat primary acquired melanosis involving the left inferior forniceal and palpebral conjunctiva. Over the ensuring 12 years, the patient experienced multiple recurrences of invasive malignant melanoma that emerged from the progressive primary acquired melanosis. Two of these recurrences were composed of nonpigmented spindle cells, and in the most florid invasive malignant melanoma that developed, the spindle cells formed a nodule 7.5 mm thick. The spindle cells were organized into fascicles and small bundles, the latter separated by a loose stroma that was devoid of mucopolysaccharides. The fascicular and neuroidal features in this case were sufficiently well developed to suggest the incorrect diagnosis of a neural tumor or a neurofibroma. However, the presence of intraepithelial atypical melanocytes at the edge of the spindle cell lesion, the absence of mucopolysaccharides in the stroma, the mitotic activity, and the absence of intercellular reticulin fibers favored the diagnosis of a spindle cell invasive malignant melanoma. This morphologic variant of conjunctival melanoma is compared with related cutaneous lesions of melanoma featuring a spindle cell population.

Visible corneal nerve fibers and neuromas of the conjunctiva--a syndrome of type-3 multiple endocrine adenomatosis in two generations.

A case report of multiple mucosal neuroma syndrome (multiple endocrine adenomatosis type 3) is presented in a mother and her two children. In all of them the eye involvement consisted of highly visible corneal nerves, neuromas of the conjunctiva, and thickened eye lids. The mother had mucosal neuromas of the tongue, and in the 4-year-old girl these were seen to appear during the follow-up period. The mother and children had medullary carcinoma of the thyroid. Marfanoid physiognomy was also one characteristic clinical feature.

Malignant melanoma of the conjunctiva.

The clinicopathological features of 37 patients with invasive melanoma of the conjunctiva have been studied. Prognosis was closely related to the subsite and size of the primary tumour. Twenty of 21 patients with small localized bulbar neoplasms (95%) and four of six patients with diffuse bulbar melanomas (67%) have survived with no evidence of secondary spread. By contrast, only one of six patients with neoplasms involving the fornix (17%) and two of four (50%) with caruncular melanomas have survived. Metastatic spread was very uncommon in patients with melanomas less than 1.5 mm in maximum thickness, but the outcome of the disease in patients with tumours greater than 1.5 mm was not always bad. Treatment by local excision biopsy was followed by a high rate of conjunctival recurrence (59%). Exenteration of the affected eye guarded against the development of further orbital disease, but was not infrequently followed by the appearance of metastases. Many (62%) of the tumours appeared to have arisen in a pre-existing melanotic lesion or pigmented naevus of long-standing. Histologically, the tumours could be divided into those with an adjacent intra-epithelial component, manifest as atypical melanocytic hyperplasia in the conjunctival epithelium adjacent to the invasive melanoma, and those without (nodular melanoma). However, clear separation of the former group into the subtypes described for cutaneous melanomas proved impossible. Prognosis was not related to the type of melanoma, mitotic rate, cell type or degree of pigmentation.

Hemangiopericytoma of the conjunctiva. Two cases.

Two patients with hemangiopericytoma of the conjunctiva are reported. The first patient, a 40-year-old woman with a six-month history of a conjunctival mass, presented with a lesion confined to the conjunctiva. The second patient, a 43-year-old man, presented with a one-year history of a conjunctival mass. Excisional biopsy and histopathologic examination showed both lesions to be a hemangiopericytoma; an uncommon tumor of the conjunctiva.