title: Satellite in transit metastases in rapidly fatal conjunctival melanoma: implications for angiotropism and extravascular migratory metastasis (description of a murine model for conjunctival melanoma).
abstract: Little information is currently available concerning loco-regional metastases such as satellite and in transit metastases and their natural history in conjunctival melanoma as compared to cutaneous melanoma. Angiotropism, a marker of extravascular migration of melanoma cells along vascular channels, often appears responsible for microscopic satellite, satellite and in transit metastases development in cutaneous melanoma. In addition, diffuse tissue microscopic satellites are correlated with widespread melanoma dissemination and death. Herein we report rapid conjunctival melanoma progression and a fatal outcome in four of five patients following recurrence as satellite in transit metastases. Five patients aged 31, 60, 63, 56, and 67 years developed primary conjunctival melanoma, histologically characterised by tumour thicknesses of 4, 4, 1.1, 3, and 2 mm. Two or more conjunctival melanomas manifested ulceration, significant mitotic rates, necrosis, angiotropism, and intralesional transformation. The conjunctival melanoma recurred in a matter of months as one or more discrete satellite in transit lesions in the vicinity of the primary melanoma. Histological examination revealed well-defined micronodules containing atypical melanocytes in the subepithelial connective tissue stroma. All lesions were extravascular and most appeared angiotropic. Four of five patients subsequently developed parotid or other loco-regional nodal disease and rapidly ensuing widespread metastases and death. The time course from diagnosis to the demise of the patients averaged about 13 (range 7-20) months. Our findings suggest that satellite in transit metastases constitute an important new risk marker for possible rapid metastatic disease progression and death in patients with conjunctival melanoma. This finding appears to take on even greater significance if such lesions develop rapidly, i.e., in a matter of weeks or months following diagnosis of primary conjunctival melanoma, and if the primary melanoma manifests additional high-risk features. Additional studies are underway in order to further elucidate the mechanism of these metastases.
authors.affiliation: Department of Pathology, Institut Curie, Paris, France. Electronic address: raymond.barnhill@gmail.com.
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Barnhill
authors.affiliation: Department of Ophthalmology, Institut Curie, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lemaitre
authors.affiliation: Department of Ophthalmology, Institut Curie, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Lévy-Gabrielle
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris, France.
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodrigues
authors.affiliation: Department of Ophthalmology, Institut Curie, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Desjardins
authors.affiliation: Department of Radiation Therapy, Institut Curie, Paris, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Dendale
authors.affiliation: Department of Pathology, Institut Curie, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
authors.affiliation: Department of Translational Research, Institut Curie, Paris, France.
authors.forename: Sergio
authors.initials: S
authors.lastname: Roman-Roman
authors.affiliation: Department of Translational Research, Institut Curie, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Lugassy
authors.affiliation: Department of Ophthalmology, Institut Curie, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cassoux
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D003230:Conjunctival Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D005123:Eye / Q000473:pathology; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000235:genetics / Q000556:secondary / Q000628:therapy; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009336:Necrosis; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D023041:Xenograft Model Antitumor Assays; D000096142:Cutaneous Malignant Melanoma
keywords: Conjunctival melanoma; angiotropism; extravascular migratory metastasis; in transit metastasis; melanoma; metastasis; microscopic satellite; satellite