Modifications of Callender's Classification of Uveal Melanoma at the Armed Forces Institute of Pathology.

One hundred well-documented cases of uveal melanoma accessioned at the Armed Forces Institute of Pathology before 1970 were reviewed and reclassified to identify changes made in the Callender classification. We compared the new classification with the original classification to determine the effect of the changes on the prediction of outcome for the patient after enucleation. Staff pathologists had originally classified 52 of the 100 cases as spindle-cell type melanoma. Only 31 of the 100 cases were reclassified as spindle-cell types (two spindle-cell nevi and 29 spindle-cell melanomas). Tumors classified as mixed-cell type were further subdivided into groups based on the percentage and size of the epithelioid cells. Tumors formerly classified as spindle-cell type that contained small or rare epithelioid cells were reclassified as mixed-cell type. This improved the prediction of outcome for the patient. We found that nucleolar size and pleomorphism are important variables that should be considered in the classification of uveal melanomas.

Diagnosis of limited ophthalmic Wegener granulomatosis: distinctive pathologic features with ANCA test confirmation.

PURPOSE: To describe the clinical and histopathologic finding of very limited ophthalmic Wegener granulomatosis (WG). METHODS: Thirteen patients with scleritis, orbitopathy, episcleritis, and panuveitis were studied. They presented without evidence of lung or kidney disease, though eight had sinus involvement. We reviewed the biopsies for histopathologic findings consistent with WG, and tested for antineutrophil cytoplasmic antibodies antineutrophil cytoplasmic antibody (ANCA). RESULTS: WG was suggested by granulomatous foci, collagen necrosis, neutrophils/nuclear dust, plasma cells and infiltrating eosinophils. Granular degeneration of the interstitial collagen; mummification of the collagen with disappearance of fibroblastic nuclei; and a polymorphous infiltrate exhibiting plasma cells, lymphocytes, neutrophils, and eosinophils within the epithelioid granulomas should suggest the diagnosis. ANCA test results supported the diagnosis of WG in all cases. CONCLUSION: The described histologic characteristics are highly suggestive of WG. These findings along with clinical or laboratory findings, allow the diagnosis of very limited ophthalmic WG in the absence of systemic involvement.

Bilateral diffuse melanocytic proliferation associated with ovarian carcinoma and metastatic malignant amelanotic melanoma.

PURPOSE: To report a case of metastatic malignant amelanotic melanoma to the skin from a patient diagnosed with bilateral diffuse uveal melanocytic proliferation (BDUMP). This dermatological finding is a unique phenomenon associated with BDUMP. DESIGN: Retrospective case report. METHODS: We studied the case of a 66-year-old Caucasian woman with gradual onset of blurred vision in her right eye followed by her left eye. She had previously been diagnosed with ovarian carcinoma, and findings of funduscopic examinations were consistent with BDUMP. Metastatic examination revealed no evidence of liver involvement. Clinical and histopathological examinations of both enucleated eyes were consistent with BDUMP. RESULTS: The hematoxylin and eosin, S-100, and HMB-45 stains were consistent with metastatic malignant amelanotic melanoma to the skin. CONCLUSIONS: Although believed to have a low potential for metastasis, patients should be monitored and evaluated regularly to detect any new lesions not associated with their primary inciting carcinoma.

Correlation of comparative genomic hybridization results of 100 archival uveal melanomas with patient survival.

Comparative genomic hybridization (CGH) was used to elucidate DNA sequence copy number imbalances in 100 archival formalin-fixed, paraffin-embedded (FFPE) uveal melanoma cases. Of these 100 cases, 51 were from patients who survived >or=9 years post diagnosis without evidence of metastasis; the remaining 49 patients died from metastatic disease. Viable probe was generated from 82 of the 100 cases, allowing correlation of CGH findings with survival for all but 18 cases. Copy number imbalances revealed by CGH were tested for univariate prognostic significance. The most powerful predictor of a poor prognosis was gain of 18q11.2, which was subsequently compared with other significant chromosomal regions, as well as histologic and clinical factors, in a multivariate analysis. There was also evidence of differential X chromosome involvement in the survival correlations between male and female cases, which may be of significance to prognosis. This large-scale CGH analysis of archival material is intended to direct further gene-specific study of malignancy in uveal melanoma.

Molecular cytogenetic evaluation of 10 uveal melanoma cell lines.

Uveal melanoma is the most common intraocular tumor in adults and often results in unilateral blindness and/or death. Previous cytogenetic characterizations of this tumor consistently revealed chromosomal abnormalities involving chromosomes 3, 6, and 8; reports of other abnormalities vary in frequency. We defined cytogenetic abnormalities of this tumor using complementary in situ hybridization techniques on 10 uveal melanoma cell lines. Synthesis of comparative genomic hybridization (CGH) and spectral karyotyping (SKY) results revealed that chromosomal rearrangement is involved in DNA sequence copy number abnormalities throughout the genome, but monosomy 3 was not found. Monosomy 3 is thought to be a significant prognostic indicator, so its absence was investigated further. Fluorescence in situ hybridization (FISH) for chromosome 3 revealed approximately 1 centromere signal per cell, but probes for 3p and 3q revealed multiple telomere signals per cell, suggesting chromosomal rearrangement without whole-chromosome loss. Based on combined CGH, SKY, and FISH data, we propose that chromosome 3 is more frequently involved in chromosomal rearrangements than whole-chromosome loss in uveal melanoma. Future approaches should be designed to confirm and enhance the resolution of regions of imbalance in primary tumors. Once identified, conserved chromosomal alterations that contribute to uveal melanoma may reveal the underlying aspects of uveal melanoma onset, metastasis and resistance to current treatment modalities.

Pathological and prognostic features of uveal melanomas.

Uveal melanomas may arise in the iris, ciliary body or choroid. Choroidal melanomas are the most common and usually display a discoid, collar-button or mushroom-shaped growth pattern. Uveal melanomas are composed of spindle and epithelioid cells and are classified histopathologically as either spindle-cell-type or mixed-cell-type tumours. The most important factors predicting clinical behaviour and underlying biology are cell type, cytomorphometric features, largest tumour dimension, scleral invasion and mitotic figures. Other valuable prognostic factors are tumour-infiltrating lymphocytes and macrophages, and the presence of vascular loops.

Cyclooxygenase-2 expression in uveal melanoma: novel classification of mixed-cell-type tumours.

BACKGROUND: The expression of cyclooxygenase-2 (COX-2), an inducible prostaglandin (PG) synthase, has been investigated in various human malignant diseases, such as cutaneous melanoma. We investigated the expression of COX-2 in uveal melanoma and related the findings to prognostic factors. METHODS: In 40 cases of uveal melanoma, immunostaining for COX-2 was done. COX-2 expression was related to histopathological prognostic markers, such as cell type, the presence of lymphocytic infiltration and vascular closed loops in the tumour, and cytomorphometry results. RESULTS: COX-2 expression was found in 58% of the cases, and it correlated with markers of poor prognosis, such as epithelioid cell type and the presence of lymphocytic infiltration and vascular closed loops. The uveal melanomas expressing COX-2 had larger nuclei, as determined by cytomorphometry. INTERPRETATION: Whereas epithelioid tumours carry a worse prognosis than spindle cell tumours, until now it has not been possible to give a strong indication of prognosis in mixed-cell tumours. This study showed that mixed-cell tumours, representing the majority of uveal melanomas, may be further subclassified according to COX-2 expression, which serves as a marker of poor prognosis. The role of COX-2 in uveal melanoma should be further elucidated, and the use of COX-2 inhibitors warrants investigation as adjuvant treatment for this life-threatening malignant disease.

Histiocytoid variant of eccrine sweat gland carcinoma of the eyelid and orbit: report of five cases.

OBJECTIVE: To study the clinicopathologic features of the histiocytoid variant of adenocarcinoma of the eccrine sweat gland of the eye and orbit. DESIGN: Retrospective case series. PARTICIPANTS: Five patients undergoing orbital and eyelid biopsy as a diagnostic procedure. METHODS: The authors examined the clinical histories and pathologic findings of five patients with eccrine adenocarcinoma of the eyelid with orbital invasion. MAIN OUTCOME MEASURES: Clinical and histopathologic examinations, including routine histopathology, immunohistochemistry, and electron microscopy studies. RESULTS: The tumors presented as insidious, diffusely infiltrative, firm cutaneous masses in the periocular area that later infiltrated the orbit. Histopathologic examination revealed that the tumors infiltrated the dermis and were composed of cells with a histiocytic to signet ring appearance. Tumor cells exhibited intracellular mucin production. Immunohistochemical stains were positive in tumor cells for low and high molecular weight cytokeratins, carcinoembryonic antigen, and epithelial membrane antigen. Electron microscopic examination showed lumen formation and intracytoplasmic mucin in tumor cells. CONCLUSIONS: The histiocytoid variant of adenocarcinoma of the eccrine sweat gland of the eyelid may present as an insidious tumor and diffusely invade the orbit. These cases may be confused with metastatic adenocarcinoma.