Feline melanoma

© S. H. Smith, M. H. Goldschmidt and P. M. McManus. A Comparative Review of Melanocytic Neoplasms. Vet Pathol 39:651-678 (2002). http://www.vetpathology.org/cgi/content/full/39/6/651

A diagnosis of melanoma in domestic animals typically carries a grave prognosis. It is generally detected at a late stage when excision is rarely curative and metastasis is often already detectable within regional lymph nodes (LN). In dogs it is a common diagnosis, accounting for 7% of all malignant tumors.50 It is the most common malignant neoplasm of the oral cavity and the second most frequent subungual neoplasm.148 In cats it is not as common but carries the same poor prognosis. In gray horses melanoma is so common as to be considered almost inevitable.150 In humans the cutaneous form of melanoma is expected to reach an incidence of 1 in 75 among individuals born in the year 2000.2 Although oral melanoma is not common in humans, accounting for only 1–2% of all melanomas, as in domestic animals, it is generally very advanced when detected and has only a 5% 5-year survival rate.203

Melanoma is uncommon in cats, accounting for less than 1% of all feline oral neoplasms90,155,220 and approximately 0.5% of feline skin tumors.32,64,86,182 The ocular and cutaneous forms are generally more common than melanoma of the oral cavity.57,64,73,182 The most common cutaneous sites are head (Fig. 5), tail, distal extremities,144 and lumbar area.57,89,90,243 The prognosis is generally poor because of recurrence and regional metastasis in up to half the cases.90,243 In a study of 23 cats with non-ocular melanocytic tumours, approximately half were malignant, including all the three oral tumours included in the study.144 In another study, four of the six reported cases of oral melanocytic tumours were malignant, with metastasis to viscera in one case and local invasion in three.182

Melanoma on medial canthus of eyelid margin in a cat Melanoma. Skin of dorsal skull between ears; feline. Exophytic, crusted, discrete mass elevating the epidermis.
Oral malignant melanoma, cat. Courtesy of Dr. Ben Colmery III Oral malignant melanoma, radiographic appearance, cat. Courtesy of Dr. Ben Colmery III
Large soft-tissue mass around the left eye of an adult female Balinese cat. The skin incision had been made prior to presentation in an attempt to lance a suspected abscess.
Spindle-shaped cells with anisokaryosis, anisocytosis, large prominent nucleoli (arrowheads), and scattered dark cytoplasmic granules (Wright-Giemsa stain). The very dark cell with cytoplasmic vacuoles (thin arrow) is a melanophage. Bar = 20 μm.
Computerized tomography (CT) imaging of a Balinese cat with a large periorbital irregularly contrast-enhancing mass (asterisks), compressing and distorting the left eye, and invading into the left nasal cavity (arrowheads 1) and nasopharynx (arrowhead 2). The round structures in the mouth are the tracheal tube (large) and esophageal stethoscope (small).

Ocular melanoma tends to occur in the anterior uveal tract, originating within the iris, with one study reporting over 60% of all feline ocular melanocytic tumors at this site.1,57,182 It typically presents as focal to diffuse iris hyperpigmentation rather than a discrete nodule or mass.65,123 Glaucoma is a common sequela.65 Melanoma originating in the limbus, conjunctiva, and nictitating membrane have also been reported, although they are very rare.22,49,199 Harris and Dubielzig (1999)107 have observed an atypical form of feline intraocular melanoma that arises multifocally in parts of the uveal tract other than the iris and tends to invade both the globe and the sclera. Ocular melanomas can be locally infiltrative or may metastasize widely.1,18,182 Some authors have documented a slow growth rate, with a long latent period between detection of primary ocular tumour and occurrence of metastatic disease.1,57,65 Others suggest that metastasis can occur in earlier stages, although this may depend on time of diagnosis and method of treatment.18,182 Melanomas with metastatic behaviour have also been described in the palpebral area,182 in the nictitans,199 and, although normally benign, in the limbus.22,57 In a study of 34 cats with diffuse iris melanoma, the overall survival time after enucleation for diffuse iris melanoma was significantly shortened relative to healthy cats and cats with enucleation for other reasons.123 Cats with disease confined to the iris stroma and trabecular meshwork (early disease) had survival times comparable with the controls, but survival times shortened with invasion into the ciliary body (moderate disease) and were shorter still with advanced disease.

The age-range is comparable in several surveys, affecting cats from 2 to 18 years of age but peaking at 8 to 12 years.57,84,86,144,182,243 No sex or breed predilection has been demonstrated.

Fig. 6. Melanoma. Skin; canine. The dermal neoplastic cells are fusiform and epithelioid. Melanocytic hyperplasia is evident in the epidermis, but it is non-neoplastic. HE. Bar = 40 µm.
Fig. 7. Melanoma. Oral; canine. Pagetoid infiltration of oral mucosa by individual cells and nests of cells (arrows) and neurotization of submucosal neoplasm. HE. Bar = 40 µm.

Criteria of malignancy

Melanoma may be one of the few neoplasms in animals for which location is an important prognostic indicator in its own right. Melanocytic neoplasias involving the oral cavity, subungual region, and mucocutaneous junctions are considered malignant, regardless of any other single feature.7 Interestingly, this also seems to be the case with oral melanoma in humans. There is no evident relationship between histologic characteristics, including mitotic index and pigmentation, and survival rate.70,190 The prognosis for human melanoma at mucocutaneous junctions and mucosal surfaces is also grave.203

In animal skin and eye melanocytic neoplasms, the most reliable histologic feature for distinguishing malignant from benign is the mitotic index.25,26,35,65,158,254 In the World Health Organization's Histologic Classification of Epithelial and Melanocytic Skin Tumours of Domestic Animals,88 three or more mitotic figures per 10 high-power fields indicate malignancy. The identification of mitotic figures in sections must be undertaken with great care to ensure that only true mitoses are counted. Bleached sections should be used for pigmented neoplasms to avoid confusing mitoses with pyknotic nuclei and the small hyperchromatic nuclei of the spindle cells of the supporting stroma. The mitotic count will vary from area to area within the neoplasm, and the count should be performed in areas with the greatest concentration of mitotic figures. Where metastases have been confirmed, the mitotic rate in intraocular melanoma is usually greater than four per 10 high-power fields; less than two mitotic figures per 10 high-power fields is consistent with a melanocytoma.35,254 In cats the value of mitotic activity to prediction of outcome is less clear, particularly with regard to ocular melanoma.21,22,65 Some authors, however, report a link between high mitotic index and increased risk of metastatic disease.57,68

Neoplastic cell morphology is also a useful discriminating feature.25,69,88 Cytologic features of malignancy include the presence of a large nucleus, variation in nuclear size and shape, hyperchromasia, abnormal chromatin clumping, one or more nucleoli, and atypical mitotic figures.65,86 Additional features favouring malignancy are the presence of neoplastic cells, individually or in nests, within the upper layers of the epidermis (Fig. 7),65,86,88 although ulceration and necrosis may prevent evaluation of this feature. The presence or absence of junctional activity is not specific to melanoma and often occurs in melanocytomas.

The gold standard is, of course, lymphatic or vascular invasion.88 Pathologists are often asked to evaluate mandibular LN for evidence of metastatic disease in dogs with oral melanoma. These nodes may be pigmented because of metastatic melanoma or the accumulation of melanophages within the medullary sinuses. The latter occurs when melanophages are transported to the regional LN after inflammation of the oral mucosa, particularly in dogs with pigmented oral epithelium. The cytologic features described above, when used to evaluate bleached sections, usually suffice to distinguish melanophages from melanoma.

In cats the following histologic features have been proposed to be of significance in identifying cutaneous melanoma: nuclear atypia (neoplasms with more extensive atypia are more likely to be malignant), mitotic activity (a trend of greater malignancy with increased numbers of mitoses), and tumour cell type (with epithelioid more likely to be malignant).89 The relationship with cell type is not firmly established in the literature, in that two studies indicate a less precise relationship between cell type and malignant potential.144,155 Furthermore, histologic determination of malignancy does not consistently correlate with clinical behavior.144

The Callender system has been used historically to determine malignant potential in canine anterior uveal melanocytic neoplasms.158,254 This system was designed to predict the behaviour of ocular melanoma in humans,37 which led to criticisms of its use in the veterinary literature for two main reasons. Firstly, it was designed for malignant tumours in humans, and most canine intraocular melanocytic tumours are benign.234,254 Secondly, the morphology of the canine neoplastic melanocytes does not match the cell descriptions in the Callender classification.35,158,254 Several authors favour a simpler system, dividing intraocular melanocytic tumours into benign and malignant using well-recognized cytologic features of malignancy as a basis for this classification.158,254 Despite these controversies, some useful morphologic features can be used to ascribe malignancy, especially with canine anterior uveal melanoma. A greater risk of metastasis tends to occur in mixed and epithelioid cell types.206 Melanocytic neoplasms containing narrow spindle-shaped cells with small nuclei and no mitotic figures, or plump cells with large amounts of melanin and small round nuclei, are more likely to be benign.81 This is in contrast to the cat where cellular pleomorphism, degree of pigmentation, nuclear to cytoplasmic ratio, and number of nucleoli bear no relationship to the metastatic behaviour of uveal melanocytic tumors.68

Tumor size,26,80,105,200 degree of pigmentation, intensity of proliferating cell nuclear antigen (PCNA)–staining,200 the presence of necrosis, ulceration, or inflammation,26,80,254 and p53 expression201 are of limited prognostic value in animals. Depth of tumour invasion into the skin is an important criterion in human medicine but is felt to be too impractical in animals.69 More sophisticated techniques, such as flow cytometry to detect chromosomal anomalies, offer no real advantage over histology in predicting tumor behavior.25,112 The value of determination of a proliferative index using MIB-1, a monoclonal antibody to Ki-67, which identifies proliferating cells, has been investigated. One study examined 27 canine and feline melanocytic tumours, eight benign and 19 malignant, to correlate Ki-67 and PCNA activity with 6-month survival.200 Ki-67 activity correlated very well with poor survival but so did the presence of invasive growth and classification based on cytologic criteria. PCNA was significantly higher in malignant neoplasms, but levels did not demonstrate a strong correlation with poor survival. In a separate study, MIB-1 was applied to 68 cutaneous canine melanocytic neoplasms to determine if the level of immunoreactivity would correlate with 2-year survival. Eighteen of 68 tumours were classed as malignant histologically. The predictive value of the Ki-67 index for 2-year survival was 97%, which was only slightly higher than the predictive value associated with histologic evaluation (91%).133

Differential diagnosis

Other tumours can look clinically very similar to melanoma, particularly those arising from the skin. These include melanocytoma as well as pigmented lesions of the epidermis and adnexa, e.g., feline basal cell tumours and carcinomas, trichoblastoma, trichoepithelioma, pilomatricoma, sebaceous, and apocrine neoplasms. Ceruminous cysts in the feline may be mistaken for multicentric melanoma of the pinna. Melanocytic hyperplasia (lentigo simplex) on the lips, eyelids, nose, and gingiva of orange, cream, and silver cats appear as pigmented macules at these sites. Hyperpigmented macular lesions clinically resembling melanoma may occur in the skin in dogs, primarily the abdomen and nipple. Similarly, epidermal hamartomas (pigmented epidermal nevi, canine seborrheic keratosis), and dermal hemangioma and hemangiosarcoma can appear as pigmented cutaneous tumors.87,88

Non-melanocytic neoplasms that commonly arise in the oral cavity and eye seldom present clinically as pigmented tumours; therefore, pigmentation is not a distraction.

  1. Acland GM, McLean IW, Aguirre GD, Trucksa R: Diffuse iris melanoma in cats. J Am Vet Med Assoc 176:52-56, 1980[Medline]
  2. Ahmed I: Malignant melanoma: prognostic indicators. Mayo Clin Proc 72:356-361, 1997[Medline]
  3. Akutsu Y, Jimbow K: Development and characterization of a mouse monoclonal antibody, MoAb HMSA-1, against a melanosomal fraction of human malignant melanoma. Cancer Res 46:2904-2911, 1986[Medline]
  4. Almeida MM, Nunes AM, Frable WJ: Malignant melanoma of soft tissue. A report of three cases with diagnosis by fine needle aspiration cytology. Acta Cytol 38:241-246, 1994[Medline]
  5. Andre JP, Delverdier M, Cabanie P, Bartel G: Malignant melanoma in an African Grey Parrot (Psittacus erithacus erithacus). J Assoc Avian Vet 7:83-85, 1993
  6. Angeli S, Koelma IA, Fleuren GJ, Van Steenis GJ: Malignant melanoma in fine needle aspirates and effusions. An immunocytochemical study using monoclonal antibodies. Acta Cytol 32:707-712, 1988[Medline]
  7. Aronsohn MG, Carpenter JL: Distal extremity melanocytic nevi and malignant melanomas in dogs. J Am Anim Hosp Assoc 26:605-612, 1990
  8. Baker JR, Leyland A: Histological survey of tumours in the horse, with particular reference to those of the skin. Vet Rec 96:419-422, 1975[Abstract]
  9. Baker R, Lumsden JH: The skin. In: Color Atlas of Cytology of the Dog and Cat, ed. Baker R, and Lumsden JH, pp 39-70, Mosby, Inc, St Louis, MO 1999
  10. Baker R, Lumsden JH: The head and neck—oropharynx, tonsils, salivary gland and thyroid. In: Color Atlas of Cytology of the Dog and Cat, ed. Baker R, and Lumsden JH, pp 117-130, Mosby, Inc, St Louis, MO 1999
  11. Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, Fleming ID, Gershenwald JE, Houghton A Jr, Kirkwood JM, McMasters KM, Mihm MF, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA, Thompson JF: Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19:3635-3648, 2001[Abstract/Free Full Text]
  12. Bar-Eli M: Molecular mechanisms of melanoma metastasis. J Cell Physiol 173:275-278, 1997[CrossRef][Medline]
  13. Barker BF, Carpenter WM, Daniels TE, Kahn MA, Leider AS, Lozada-Nur F, Lynch DP, Melrose R, Merrell P, Morton T, Peters E, Regezi JA, Richards SD, Rick GM, Rohrer MD, Slater L, Stewart JC, Tomich CE, Vickers RA, Wood NK, Young SK: Oral mucosal melanomas: the WESTOP Banff workshop proceedings. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 83:672-679, 1997[CrossRef][Medline]
  14. Barnett KC, Platt H: Intraocular melanomata in the horse. Equine Vet J 10: (Suppl) 76-82, 1990
  15. Basler GC, Fader DJ, Yahanda A, Sondak VK, Johnson TM: The utility of fine needle aspiration in the diagnosis of melanoma metastatic to lymph nodes. J Am Acad Dermatol 36:403-408, 1997[CrossRef][Medline]
  16. Beaty MW, Fetsch P, Wilder AM, Marincola F, Abati A: Effusion cytology of malignant melanoma. A morphologic and immunocytochemical analysis including application of the MART-1 antibody. Cancer 81:57-63, 1997[CrossRef][Medline]
  17. Beck ER, Withrow SJ, McChesney AE, Richardson RC, Henderson RA, Norris AM, Caywood DD, Klausner JS, Harvey HJ, Holmberg DL: Canine tongue tumors: a retrospective review of 57 cases. J Am Anim Hosp Assoc 22:525-532, 1986
  18. Bellhorn RW, Henkind P: Intra-ocular malignant melanoma in domestic cats. Trans Ophthalmol Soc UK 89:321-333, 1970[Medline]
  19. Ben Romdhane K, Khattech R, Ben Othman M, Gamoudi A, Ammar A, Cammoun M: Melanin production in medullary thyroid carcinoma. Histopathology 27:569-571, 1995[Medline]
  20. Berrington AJ, Jimbow K, Haines DM: Immunohistochemical detection of melanoma-associated antigens on formalin-fixed, paraffin-embedded canine tumors. Vet Pathol 31:455-461, 1994[Abstract]
  21. Bertoy RW, Brightman AH, Regan K: Intraocular melanoma with multiple metastases in a cat. J Am Vet Med Assoc 192:87-89, 1988[Medline]
  22. Betton A, Healy LN, English RV, Bunch SE: Atypical limbal melanoma in a cat. J Vet Intern Med 13:379-381, 1999[CrossRef][Medline]
  23. Bizjak-Schwarzbartl M: Fine-needle aspiration biopsy in the diagnosis of metastases in the liver. Diagn Cytopathol 3:278-283, 1987[Medline]
  24. Black WC, Wiggins C: Melanoma among southwestern American Indians. Cancer 55:2899-2902, 1985[CrossRef][Medline]
  25. Bolon B, Calderwood-Mays MB, Hall BJ: Characteristics of canine melanomas and comparison of histology and DNA ploidy to their biologic behavior. Vet Pathol 27:96-102, 1990[Abstract]
  26. Bostock DE: Prognosis after surgical excision of canine melanomas. Vet Pathol 16:32-40, 1979[Abstract]
  27. Bottger D, Dowden RV, Kay PP: Complete spontaneous regression of cutaneous primary malignant melanoma. Plast Reconstr Surg 89:548-553, 1992[Medline]
  28. Brantley MA Jr, Harbour JW: Deregulation of the Rb and p53 pathways in uveal melanoma. Am J Pathol 157:1795-1801, 2000[Abstract/Free Full Text]
  29. Breslow A: Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 172:902-908, 1970[Medline]
  30. Brochez L, Naeyaert JM: Serological markers for melanoma. Br J Dermatol 143:256-268, 2000[CrossRef][Medline]
  31. Brodey RS: A clinical and pathologic study of 130 neoplasms of the mouth and pharynx in the dog. Am J Vet Res 21:787-812, 1960
  32. Brodey RS: The biological behavior of canine oral and pharyngeal neoplasms. J Small Anim Pract 11:45-53, 1970[Medline]
  33. Brodland DG: The life of a skin cancer. Mayo Clin Proc 72:475-478, 1997[Medline]
  34. Burchill SA, Bennett DC, Holmes A, Thody AJ: Tyrosinase expression and melanogenesis in melanotic and amelanotic B16 mouse melanoma cells. Pathobiology 59:335-339, 1991[CrossRef][Medline]
  35. Bussanich NM, Dolman PJ, Rootman J, Dolman CL: Canine uveal melanomas: series and literature review. J Am Anim Hosp Assoc 23:415-422, 1987
  36. Byers HR, Bhawan J: Pathologic parameters in the diagnosis and prognosis of primary cutaneous melanoma. Hematol Oncol Clin North Am 12:717-735, 1998[CrossRef][Medline]
  37. Callender GR: Malignant melanotic tumors of the eye. A study of histologic types in 111 cases. Trans Am Acad Ophthalmol Otolaryngol 36:131-142, 1931
  38. Canella KA, Diwan BA, Gorelick PL, Donovan PJ, Sipowicz MA, Kasprzak KS, Weghorst CM, Snyderwine EG, Davis CD, Keefer LK, Kyrtopoulos SA, Hecht SS, Wang M, Anderson LM, Rice JM: Liver tumorigenesis by Helicobacter hepaticus: considerations of mechanism. In Vivo 10:285-292, 1996[Medline]
  39. Cangiarella J, Symmans WF, Cohen JM, Goldenberg A, Shapiro RL, Waisman J: Malignant melanoma metastatic to the breast: a report of seven cases diagnosed by fine-needle aspiration cytology. Cancer 84:160-162, 1998[CrossRef][Medline]
  40. Cangiarella J, Symmans WF, Shapiro RL, Roses DF, Cohen JM, Chhieng D, Harris MN, Waisman J: Aspiration biopsy and the clinical management of patients with malignant melanoma and palpable regional lymph nodes. Cancer 90:162-166, 2000[CrossRef][Medline]
  41. Char DH, Kroll SM, Stoloff A, Kaleta-Michaels S, Crawford JB, Miller TR, Howes EL, Ljung BM: Cytomorphometry of uveal melanoma. Comparison of fine needle aspiration biopsy samples with histologic sections. Anal Quant Cytol Histol 13:293-299, 1991[Medline]
  42. Chénier S, Doré M: Oral malignant melanoma with osteoid formation in a dog. Vet Pathol 36:74-76, 1999[Abstract]
  43. Cheville NF: Extracellular substances, pigments and crystals. In: Ultrastructural Pathology, ed. Cheville NF, 1st ed., pp 276-326, Iowa State University Press, Ames, IA 1994
  44. Chhieng DC, Cangiarella JF, Waisman J, Cohen JM: Fine-needle aspiration cytology of desmoplastic malignant melanoma metastatic to the parotid gland: case report and review of the literature. Diagn Cytopathol 22:97-100, 2000[CrossRef][Medline]
  45. Clark WH Jr, Elder DE, Guerry D: Dysplastic nevi and malignant melanoma. In: Pathology of the Skin, ed. Farmer ER, and Hood AF, pp 684-756, Appleton & Lange, Norwalk, CT 1990
  46. Clark WH Jr, Elder DE, Guerry D 4th, Braitman LE, Trock BJ, Schultz D, Synnestvedt M, Halpern AC: Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst 81:1893-1904, 1989[Abstract/Free Full Text]
  47. Collinson PN, Peiffer RL: Clinical presentation, morphology, and behavior of primary choroidal melanomas in eight dogs. Prog Vet Comp Ophthalmol 3:158-164, 1993
  48. Conroy JD: Melanocytic tumors of domestic animals. Arch Dermatol 96:372-380, 1967[CrossRef][Medline]
  49. Cook CS, Rosenkrantz W, Peiffer RL, MacMillan A: Malignant melanoma of the conjunctiva in a cat. J Am Vet Med Assoc 186:505-506, 1985[Medline]
  50. Cotchin E: Melanotic tumors of dogs. J Comp Path Ther 65:115-129, 1955
  51. Cotchin E: Tumours in farm animals: a survey of tumours examined at the Royal Veterinary College, London, during 1950–60. Vet Rec 72:816-823, 1960
  52. Cotran RS, Kumar V, Collins T: The female breast. In: Robbins Pathological Basis of Disease, ed. Cotran RS, 6th ed., pp 1093-1119, WB Saunders, Philadelphia, PA 1999
  53. Croxatto JO, Herrera HD, Lightowler CH: Malignant melanoma arising from primary acquired melanosis in a dog. Canine Pract 17:22-24, 1992
  54. Cui J, Chen D, Misfeldt ML, Swinfard RW, Bystryn JC: Antimelanoma antibodies in swine with spontaneously regressing melanoma. Pigment Cell Res 8:60-63, 1995[CrossRef][Medline]
  55. Dardick I: Handbook of Diagnostic Electron Microscopy for Pathologists-in-Training. pp 3.8-3.9, Igaku-Shoin Medical Publishers, Inc, Tokyo, Japan 1996
  56. Davidson HJ, Blanchard GL, Wheeler CA, Render JA: Anterior uveal melanoma, with secondary keratitis, cataract, and glaucoma, in a horse. J Am Vet Med Assoc 199:1049-1050, 1991[Medline]
  57. Day MJ, Lucke VM: Melanocytic neoplasia in the cat. J Small Anim Pract 36:207-213, 1995[Medline]
  58. De Las Casas LE, Raso DS, Baird DB, Silverman JF: FNA of malignant melanoma: a brown stain without brown stains? Diagn Cytopathol 19:151-152, 1998[CrossRef][Medline]
  59. Deerberg F, Knup F, Rehm S: Spontaneous epithelial tumours of the skin in Han:WIST- and DA/Han rats. Z Versuchstierkd 28:45-57, 1986[Medline]
  60. Diters RW, Dubielzig RR, Aguirre GD, Acland GM: Primary ocular melanoma in dogs. Vet Pathol 20:379-395, 1983[Abstract]
  61. Diters RW, Walsh KM: Canine cutaneous clear cell melanomas: a report of three cases. Vet Pathol 21:355-356, 1984[Medline]
  62. Dixon PM, Head KW: Equine nasal and paranasal sinus tumours: part 2: a contribution of 28 case reports. Vet J 157:279-294, 1999[CrossRef][Medline]
  63. Dooley TP: Recent advances in cutaneous melanoma oncogenesis research. Oncol Res 6:1-9, 1994[Medline]
  64. Dorn CR, Priester WA: Epidemiologic analysis of oral and pharyngeal cancer in dogs, cats, horses, and cattle. J Am Vet Med Assoc 169:1202-1206, 1976[Medline]
  65. Dubielzig RR: Ocular neoplasia in small animals. Vet Clin North Am Small Anim Pract 20:837-848, 1990[Medline]
  66. Dubielzig RR, Aguirre GD, Gross SL, Diters RW: Choroidal melanomas in dogs. Vet Pathol 22:582-585, 1985[Abstract]
  67. Dugan SJ: Ocular neoplasia. Vet Clin North Am Equine Pract 8:609-626, 1992[Medline]
  68. Duncan DE, Peiffer RL: Morphology and behavior of anterior uveal melanomas in cats. Prog Vet Com Ophthalmol 12:25-32, 1991
  69. Dunstan RW, Rosser EJ: Comparative aspects of cutaneous melanocytic neoplasms in the dog. Comp Dermatopathol 7:197-201, 1985
  70. Eisen D, Voorhees JJ: Oral melanoma and other pigmented lesions of the oral cavity. J Am Acad Dermatol 24:527-537, 1991[Medline]
  71. Elder DE, Murphy GF: Malignant tumors and related lesions. In: Atlas of Tumor Pathology: Melanocytic Tumors of the Skin, ed. Rosai J, pp 166-198, AFIP, Washington, DC 1991
  72. Eneroth CM: Malignant melanoma of the oral cavity. Int J Oral Surg 4:191-197, 1975[Medline]
  73. Engle CG, Brodey RS: A retrospective study of 395 feline neoplasms. J Am Anim Hosp Assoc 5:21-31, 1967
  74. Feeney-Burns L, Burns RP, Gao CL: Ocular pathology in melanomatous Sinclair miniature swine. Am J Pathol 131:62-72, 1988[Abstract]
  75. Flanders E, Kornstein MJ, Wakely PE, Kardos TF, Frable WJ: Lymphoglandular bodies in fine-needle aspiration cytology smears. Am J Clin Pathol 99:566-569, 1993[Medline]
  76. Fournel-Fleury C, Magnol J-P, Guelfi J-F: Color atlas of cancer cytology of the dog and cat. Conférence Nationale des Vétérinaires Spécialisés en Petits Animaux, Paris, France, pp 34-50, 1994
  77. Fournel-Fleury C, Magnol J-P, Guelfi J-F: Color atlas of cancer cytology of the dog and cat. Conférence Nationale des Vétérinaires Spécialisés en Petits Animaux, Paris, France, pp 83-84, 126:1994
  78. Fournel-Fleury C, Magnol J-P, Guelfi J-F: Color atlas of cancer cytology of the dog and cat. Conférence Nationale des Vétérinaires Spécialisés en Petits Animaux, Paris, France, pp 216-219, 1994
  79. Fournel-Fleury C, Magnol J-P, Guelfi J-F: Color atlas of cancer cytology of the dog and cat. Conférence Nationale des Vétérinaires Spécialisés en Petits Animaux, Paris, France, pp 257276-283, 1994
  80. Frese K: Developmental studies on melanoma of the skin and mouth mucosa of dogs. Vet Pathol 15:461-473, 1978 [In German][Abstract]
  81. Friedman DS, Miller L, Dubielzig RR: Malignant canine anterior uveal melanoma. Vet Pathol 26:523-525, 1989[Medline]
  82. Friedman M, Rao U, Fox S: The cytology of metastatic balloon cell melanoma. Acta Cytol 26:39-43, 1982[Medline]
  83. Gelatt KN, Johnson KA, Peiffer RL Jr: Primary iridal pigmented masses in three dogs. J Am Anim Hosp Assoc 15:339-344, 1979
  84. Gilger BC, McLaughlin SA, Whitley RD, Wright JC: Orbital neoplasms in cats: 21 cases (1974–1990). J Am Vet Med Assoc 201:1083-1086, 1992[Medline]
  85. Giuliano EA, Chappell R, Fischer B, Dubielzig RR: A matched observational study of canine survival with primary intraocular melanocytic neoplasia. Vet Ophthalmol 2:185-190, 1999[CrossRef][Medline]
  86. Goldschmidt MH: Benign and malignant melanocytic neoplasms of domestic animals. Am J Dermatopathol 7: (Suppl) 203-212, 1985[Medline]
  87. Goldschmidt MH: Pigmented lesions of the skin. Clin Dermatol 12:507-514, 1994[CrossRef][Medline]
  88. Goldschmidt MH, Dunstan RW, Stannard AA, von Tscharner C, Walder EJ, Yager JA: Melanocytic tumors and tumor-like lesions. In: Histological Classification of Epithelial and Melanocytic Tumors of the Skin of Domestic Animals, ed. Goldschmidt MH, Dunstan RW, Stannard AA, von Tscharner C, Walder EJ, and Yager JA, pp 38-40, Armed Forces Institute of Pathology, Washington, DC 1998
  89. Goldschmidt MH, Liu S-S, Shofer FS: Feline dermal melanoma: a retrospective study. In Advances in Veterinary Dermatology ed. Ihrke PJ, Mason IS, and White SD vol. 2: pp 285-292, Pergamon Press, Oxford, UK 1993
  90. Goldschmidt MH, Shofer FS: Skin Tumors of the Dog and Cat. pp 142-151, Butterworth Heinemann, Oxford, UK 1992
  91. Goodison S, Urquidi V, Tarin D: CD44 cell adhesion molecules. Mol Pathol 52:189-196, 1999[Abstract]
  92. Gorham S, Robl M: Melanoma in the gray horse: the darker side of equine aging. Vet Med 81:446-448, 1986
  93. Gorlin RJ, Barron CN, Chaudhry AP, Clark JJ: The oral and pharyngeal pathology of domestic animals: a study of 487 cases. Am J Vet Res 20:1032-1061, 1959
  94. Goubran GF, Adekeye EO, Edwards MB: Melanoma of the face and mouth in Nigeria. A review and comment on three cases. Int J Oral Surg 7:453-462, 1978[Medline]
  95. Gown AM, Vogel AM, Hoak D, Gough F, McNutt MA: Monoclonal antibodies specific for melanocytic tumors distinguish subpopulations of melanocytes. Am J Pathol 123:195-203, 1986[Abstract]
  96. Green A, Neale R, Kelly R, Smith I, Ablett E, Meyers B, Parsons P: An animal model for human melanoma. Photochem Photobiol 64:577-580, 1996[Medline]
  97. Greene JF Jr, Morgan CD, Rao A, Amoss MS Jr, Arguello F: Regression by differentiation in the Sinclair swine model of cutaneous melanoma. Melanoma Res 7:471-477, 1997[CrossRef][Medline]
  98. Greene JF Jr, Townsend JS 4th, Amoss MS Jr: Histopathology of regression in sinclair swine model of melanoma. Lab Invest 71:17-24, 1994[Medline]
  99. Greene MH: Genetics of cutaneous melanoma and nevi. Mayo Clin Proc 72:467-474, 1997[Medline]
  100. Greene MH: The genetics of hereditary melanoma and nevi. 1998 update. Cancer 86:2464-2477, 1999[CrossRef][Medline]
  101. Griffiths GL, Lumsden JH: Fine needle aspiration cytology and histologic correlation in canine tumors. Vet Clin Pathol 13:13-17, 1984[Medline]
  102. Gross TL, Ihrke PJ, Walder EJ: Melanocytic tumors. In: Veterinary Dermatopathology, ed. Gross TL, Ihrke PJ, and Walder EJ, pp 459-464, Mosby, Inc, St Louis, MO 1992
  103. Guo Y, Ma J, Wang J, Che X, Narula J, Bigby M, Wu M, Sy MS: Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody. Cancer Res 54:1561-1565, 1994[Medline]
  104. Gupta SK, Rajwanshi AK, Das DK: Fine needle aspiration cytology smear patterns of malignant melanoma. Acta Cytol 29:983-988, 1985[Medline]
  105. Hahn KA, Bravo L, Adams WH, Frazier DL: Naturally occurring tumors in dogs as comparative models for cancer therapy research. In Vivo 8:133-143, 1994[Medline]
  106. Hamor RE, Severin GA, Roberts SM: Intraocular melanoma in an alpaca. Vet Ophthalmol 2:193-196, 1999[CrossRef][Medline]
  107. Harris BP, Dubielzig RR: Atypical primary ocular melanoma in cats. Vet Ophthalmol 2:121-124, 1999[CrossRef][Medline]
  108. Harvey HJ, MacEwan EG, Braun D, Patnaik AK, Withrow SJ, Jongeward S: Prognostic criteria for dogs with oral melanoma. J Am Vet Med Assoc 178:580-582, 1981[Medline]
  109. Hirschberger J, DeNicola DB, Hermanns W, Kraft W: Sensitivity and specificity of cytologic evaluation in the diagnosis of neoplasia in body fluids from dogs and cats. Vet Clin Pathol 28:142-146, 1999[Medline]
  110. Honnas CM, Liskey CC, Meagher DM, Brown D, Luck EE: Malignant melanoma in the foot of a horse. J Am Vet Med Assoc 197:756-758, 1990[Medline]
  111. Hook RR, Berkelhammer J, Oxenhandler RW: Melanoma: Sinclair swine melanoma. Am J Pathol 108:130-133, 1982[Medline]
  112. Horsting N, Wohlsein P, Reimann N, Bartnitzke S, Bullerdiek J, Nolte I: Cytogenetic analysis of three oropharyngeal malignant melanomas in dogs. Res Vet Sci 67:149-151, 1999[CrossRef][Medline]
  113. Hsu MY, Meier FE, Nesbit M, Hsu JY, Van Belle P, Elder DE, Herlyn M: E-cadherin expression in melanoma cells restores keratinocyte-mediated growth control and down-regulates expression of invasion-related adhesion receptors. Am J Pathol 156:1515-1525, 2000[Abstract/Free Full Text]
  114. Hsueh EC, Lucci A, Qi K, Morton DL: Survival of patients with melanoma of the lower extremity decreases with distance from the trunk. Cancer 85:383-388, 1999[CrossRef][Medline]
  115. Huang S, Ullrich SE, Bar-Eli M: Regulation of tumor growth and metastasis by interleukin-10: the melanoma experience. J Interferon Cytokine Res 19:697-703, 1999[CrossRef][Medline]
  116. Innes DJ, Feldman PS: Comparison of diagnostic results obtained by fine needle aspiration cytology and tru-cut or open biopsies. Acta Cytol 27:350-354, 1983[Medline]
  117. Izban KF, Candel AG, Hsi ED, Selvaggi SM: Metastatic melanoma of the vulva identified by peritoneal fluid cytology. Diagn Cytopathol 20:152-155, 1999[CrossRef][Medline]
  118. Jakobiec FA, Folberg R, Iwamoto T: Clinicopathologic characteristics of premalignant and malignant melanocytic lesions of the conjunctiva. Ophthalmology 96:147-166, 1989[Medline]
  119. Jerbi G, Boussen H, Ennaifer-Jerbi E, Karboul S, Osman A, Rahal K: Melanoma arising in burn scars: report of 3 observations and a literature review. Arch Dermatol 135:1551-1553, 1999[Free Full Text]
  120. Johnson PJ: Dermatologic tumors (excluding sarcoids). Vet Clin North Am Equine Pract 14:625-658, 1998[Medline]
  121. Johnston WW: The malignant pleural effusion. A review of cytopathologic diagnoses of 584 specimens from 472 consecutive patients. Cancer 56:905-909, 1985[CrossRef][Medline]
  122. Kahn HJ, Marks A, Thom H, Baumal R: Role of antibody to S100 protein in diagnostic pathology. Am J Clin Pathol 79:341-347, 1983[Medline]
  123. Kalishman JB, Chappell R, Flood LA, Dubielzig RR: A matched observational study of survival in cats with enucleation due to diffuse iris melanoma. Vet Ophthalmol 1:25-29, 1998[CrossRef][Medline]
  124. Kirker-Head CA, Loeffler D, Held JP: Pelvic limb lameness due to malignant melanoma in a horse. J Am Vet Med Assoc 186:1215-1217, 1985[Medline]
  125. Kobayashi G, Cobb C: A case of amelanotic spindle-cell melanoma presenting as metastases to breast and axillary lymph node: diagnosis by FNA cytology. Diagn Cytopathol 22:246-249, 2000[CrossRef][Medline]
  126. Koenig A, Wojcieszyn J, Weeks BR, Modiano JF: Expression of S100a, vimentin, NSE, and Melan A/MART-1 in seven canine melanoma cell lines and twenty-nine retrospective cases of canine melanoma. Vet Pathol 38:427-435, 2001[Abstract/Free Full Text]
  127. Koh HK: Cutaneous melanoma. N Engl J Med 325:171-182, 1991[Medline]
  128. Koren R, Bernheim J, Schachter P, Schwartz A, Siegal A, Gal R: Black thyroid adenoma. Clinical, histochemical, and ultrastructural features. Appl Immunohistochem Mol Morphol 8:80-84, 2000[CrossRef][Medline]
  129. Kufuor-Mensah E, Watson GL: Malignant melanomas in a penguin (Eudyptes chrysolphus) and a red-tailed hawk (Buteo jamaicensis). Vet Pathol 29:354-356, 1992[Medline]
  130. Kunze DJ, Monticello TM, Jakob TP, Crane S: Malignant melanoma of the coronary band in a horse. J Am Vet Med Assoc 188:297-298, 1986[Medline]
  131. Lai R, Redburn J, Nguyen GK: Cytodiagnosis of metastatic amelanotic melanomas by fine-needle aspiration biopsy: adjunctival value of immunocytochemistry and electron microscopy. Cancer 84:92-97, 1998[CrossRef][Medline]
  132. Langenbach A, McManus PM, Hendrick MJ, Shofer FS, Sorenmo KU: Sensitivity and specificity of methods of assessing the regional lymph nodes for evidence of metastasis in dogs and cats with solid tumors. J Am Vet Med Assoc 218:1424-1428, 2001[CrossRef][Medline]
  133. Laprie C, Abadie J, Amardeilh MF, Net JL, Lagadic M, Delverdier M: MIB-1 immunoreactivity correlates with biologic behaviour in canine cutaneous melanoma. Vet Dermatol 12:139-147, 2001[CrossRef][Medline]
  134. Lazar-Molnar E, Hegyesi H, Toth S, Falus A: Autocrine and paracrine regulation by cytokines and growth factors in melanoma. Cytokine 12:547-554, 2000[CrossRef][Medline]
  135. Lentz KJ, Burns RP, Loeffler K, Feeney-Burns L, Berkelhammer J, Hook RR Jr: Uveitis caused by cytotoxic immune response to cutaneous malignant melanoma in swine: destruction of uveal melanocytes during tumor regression. Invest Ophthalmol Vis Sci 24:1063-1069, 1983[Abstract/Free Full Text]
  136. Lerner AB, Cage GW: Melanomas in horses. Yale J Biol Med 46:646-649, 1973[Medline]
  137. Levene A: Equine melanotic disease. Tumori 57:133-168, 1971[Medline]
  138. Li G, Herlyn M: Dynamics of intercellular communication during melanoma development. Mol Med Today 6:163-169, 2000[CrossRef][Medline]
  139. Lin EY, Piepkorn M, Garcia R, Byrd D, Tsou R, Isik FF: Angiogenesis and vascular growth factor receptor expression in malignant melanoma. Plast Reconstr Surg 104:1666-1674, 1999[Medline]
  140. Lindblom A, Liljegren A: Regular review: tumour markers in malignancies. Br J Dermatol 143:256-268, 2000[CrossRef][Medline]
  141. Lioe TF, Elliott H, Allen DC, Spence RA: The role of fine needle aspiration cytology (FNAC) in the investigation of superficial lymphadenopathy; uses and limitations of the technique. Cytopathology 10:291-297, 1999[CrossRef][Medline]
  142. Loganzo F Jr, Dosik JS, Zhao Y, Vidal MJ, Nanus DM, Sudol M, Albino AP: Elevated expression of protein tyrosine kinase c-Yes, but not c-Src, in human malignant melanoma. Oncogene 8:2637-2644, 1993[Medline]
  143. Longatto Filho A, de Carvalho LV, Santos Gda C, Oyafuso MS, Lombardo V, Bortolan J, Neves JI: Cytologic diagnosis of melanoma in serous effusions. A morphologic and immunocytochemical study. Acta Cytol 39:481-484, 1995[Medline]
  144. Luna LD, Higginbotham ML, Henry CJ, Turnquist SE: Feline non-ocular melanoma: a retrospective study of 23 cases (1991–1999). J Feline Med Surg 2:173-181, 2000[CrossRef][Medline]
  145. MacEwen EG: Spontaneous tumors in dogs and cats: models for the study of cancer biology and treatment. Cancer Metastasis Rev 9:125-136, 1990[CrossRef][Medline]
  146. MacKie RM: Malignant melanoma: clinical variants and prognostic indicators. Clin Exp Dermatol 25:471-475, 2000[CrossRef][Medline]
  147. Marcus JN, Dise CA, LiVolsi VA: Melanin production in a medullary thyroid carcinoma. Cancer 49:2518-2526, 1982[CrossRef][Medline]
  148. Marino DJ, Matthiesen DT, Stefanacci JD, Moroff SD: Evaluation of dogs with digit masses: 117 cases (1981–1991). J Am Vet Med Assoc 207:726-728, 1995[Medline]
  149. Matthews AG, Barry DR: Bilateral melanoma of the iris in a horse. Equine Vet J 19:358-360, 1987[Medline]
  150. McFadyean S: Equine melanomatosis. J Comp Med 46:186-204, 1933
  151. Meier F, Nesbit M, Hsu MY, Martin B, Van Belle P, Elder DE, Schaumburg-Lever G, Garbe C, Walz TM, Donatien P, Crombleholme TM, Herlyn M: Human melanoma progression in skin reconstructs: biological significance of bFGF. Am J Pathol 156:193-200, 2000[Abstract/Free Full Text]
  152. Meier F, Satyamoorthy K, Nesbit M, Hsu MY, Schittek B, Garbe C, Herlyn M: Molecular events in melanoma development and progression. Front Biosci 3:D1005-D1010, 1998[Medline]
  153. Meleo KA: Tumors of the skin and associated structures. Vet Clin North Am Small Anim Pract 27:73-94, 1997[Medline]
  154. Miller MA, Weaver AD, Stogsdill PL, Fischer JR: Cutaneous melanocytomas in 10 young cattle. Vet Pathol 32:479-484, 1995[Abstract]
  155. Miller WH, Scott DW, Anderson WI: Feline cutaneous melanocytic neoplasms: a retrospective analysis of 43 cases (1979–1991). Vet Dermatol 4:19-26, 1993
  156. Millikan LE, Boylon JL, Hook RR, Manning PJ: Melanoma in Sinclair swine: a new animal model. J Invest Dermatol 62:20-30, 1974[CrossRef][Medline]
  157. Milne JC: Malignant melanomas causing Horner's syndrome in a horse. Equine Vet J 18:74-75, 1986[Medline]
  158. Minami T, Patnaik AK: Malignant anterior uveal melanoma with diffuse metastasis in a dog. J Am Vet Med Assoc 201:1894-1896, 1992[Medline]
  159. Mitteldorf CA, Alves VA, Kanamura CT, Carneiro PC: Immunocytochemistry applied to aspiration biopsy cytology. Diagnostic contribution in 100 cases of previously stained, routine specimens. Acta Cytol 43:218-226, 1999[Medline]
  160. Modiano JF, Ritt MG, Wojcieszyn J: The molecular basis of canine melanoma: pathogenesis and trends in diagnosis and therapy. J Vet Intern Med 13:163-174, 1999[CrossRef][Medline]
  161. Modiano JF, Ritt MG, Wojcieszyn J, Smith R 3rd: Growth arrest of melanoma cells is differentially regulated by contact inhibition and serum deprivation. DNA Cell Biol 18:357-367, 1999[CrossRef][Medline]
  162. Morales-Ducret CR, van de Rijn M, LeBrun DP, Smoller BR: bcl-2 expression in primary malignancies of the skin. Arch Dermatol 131:909-912, 1995[Abstract]
  163. Morgan CD, Measel JW Jr, Amoss MS Jr, Rao A, Greene JF Jr: Immunophenotypic characterization of tumor infiltrating lymphocytes and peripheral blood lymphocytes isolated from melanomatous and non-melanomatous Sinclair miniature swine. Vet Immunol Immunopathol 55:189-203, 1996[CrossRef][Medline]
  164. Morgan RV, Patton CS: Choroidal melanoma in a dog. Cornell Vet 83:211-217, 1993[Medline]
  165. Mowlavi A, Malafa MP: Angiogenesis in primary tumor cells of metastatic and nonmetastatic malignant melanoma. Plast Reconstr Surg 106:514, 2000[Medline]
  166. Mulligan RM: Melanoblastic tumors in the dog. Am J Vet Res 22:345-351, 1961[Medline]
  167. Murray MJ, Cavey DM, Feldman BF, Trostle SS, White NA: Signs of sympathetic denervation associated with a thoracic melanoma in a horse. J Vet Intern Med 11:199-203, 1997[Medline]
  168. Murty TS, Rao MN, Rao TB: Malignant melanoma in a crossbred Jersey cow—a case report. Indian Vet J 72:1309, 1995
  169. Nakajima T, Watanabe S, Sato Y, Kameya T, Hirota T, Shimosato Y: An immunoperoxidase study of S-100 protein distribution in normal and neoplastic tissues. Am J Surg Pathol 6:715-727, 1982[Medline]
  170. Nakhleh RE, Wick MR, Rocamora A, Swanson PE, Dehner LP: Morphologic diversity in malignant melanomas. Am J Clin Pathol 93:731-740, 1990[Medline]
  171. Nasiell K, Tani E, Skoog L: Fine needle aspiration cytology and immunocytochemistry of metastatic melanoma. Cytopathology 2:137-147, 1991[Medline]
  172. Neitzel LT, Neitzel CD, Magee KL, Malafa MP: Angiogenesis correlates with metastasis in melanoma. Ann Surg Oncol 6:70-74, 1999[Abstract]
  173. Neubauer A, Thalmann U, Musch R, Grosser H, Loddenkemper R, Huhn D: Prospective comparison of the diagnostic value of cytology and immunocytology in pleural effusion studied by thoracoscopy and biopsy. Klin Wochenschr 65:400-406, 1987[CrossRef][Medline]
  174. Niemann TH, Thomas PA: Melanoma with signet-ring cells in a peritoneal effusion. Diagn Cytopathol 12:241-244, 1995[Medline]
  175. Oakes MG, Lewis DD, Hedlund CS, Hosgood G: Canine oral neoplasia. Comp Contin Educ Pract Vet 15:15-30, 1993
  176. Oliver JL 3rd, Wolfe LG: Antigen expression in canine tissues, recognized by a monoclonal antibody generated against canine melanoma cells. Am J Vet Res 53:123-128, 1992[Medline]
  177. Orchard GE: Comparison of immunohistochemical labelling of melanocyte differentiation antibodies melan-A, tyrosinase and HMB 45 with NKIC3 and S100 protein in the evaluation of benign naevi and malignant melanoma. Histochem J 32:475-481, 2000[CrossRef][Medline]
  178. Oxenhandler RW, Adelstein EH, Haigh JP, Hook RR Jr, Clark WH Jr: Malignant melanoma in the Sinclair miniature swine: an autopsy study of 60 cases. Am J Pathol 96:707-720, 1979[Abstract]
  179. Oxenhandler RW, Berkelhammer J, Smith GD, Hook RR Jr: Growth and regression of cutaneous melanomas in Sinclair miniature swine. Am J Pathol 109:259-269, 1982[Abstract]
  180. Parsons PG, Takahashi H, Candy J, Meyers B, Vickers J, Kelly WR, Smith I, Spradbrow P: Histopathology of melanocytic lesions in goats and establishment of a melanoma cell line: a potential model for human melanoma. Pigment Cell Res 3:297-305, 1990[CrossRef][Medline]
  181. Pathak S, Multani AS, McConkey DJ, Imam AS, Amoss MS Jr: Spontaneous regression of cutaneous melanoma in sinclair swine is associated with defective telomerase activity and extensive telomere erosion. Int J Oncol 17:1219-1224, 2000[Medline]
  182. Patnaik AK, Mooney S: Feline melanoma: a comparative study of ocular, oral, and dermal neoplasms. Vet Pathol 25:105-112, 1988[Abstract]
  183. Perniciaro C: Dermatopathologic variants of malignant melanoma. Mayo Clin Proc 72:273-279, 1997[Medline]
  184. Perry MD, Gore M, Seigler HF, Johnston WW: Fine needle aspiration biopsy of metastatic melanoma. A morphologic analysis of 174 cases. Acta Cytol 30:385-396, 1986[Medline]
  185. Perry MD, Seigler HF, Johnston WW: Diagnosis of metastatic malignant melanoma by fine needle aspiration biopsy: a clinical and pathologic correlation of 298 cases. J Natl Cancer Inst 77:1013-1021, 1986[Medline]
  186. Prehn RT: The paradoxical association of regression with a poor prognosis in melanoma contrasted with a good prognosis in keratoacanthoma. Cancer Res 56:937-940, 1996[Medline]
  187. Pulley LT, Stannard AA: Tumors of the skin and soft tissues. In: Tumors in Domestic Animals, ed. Moulton JE, 3rd ed., pp 75-82, University of California Press, Berkeley and Los Angeles, CA 1990
  188. Rabanal RH, Fondevila DM, Montane V, Domingo M, Ferrer L: Immunocytochemical diagnosis of skin tumours of the dog with special reference to undifferentiated types. Res Vet Sci 47:129-133, 1989[Medline]
  189. Ramaekers F, Haag D, Jap P, Vooijs PG: Immunochemical demonstration of keratin and vimentin in cytologic aspirates. Acta Cytol 28:385-392, 1984[Medline]
  190. Ramos-Vara JA, Beissenherz ME, Miller MA, Johnson GC, Pace LW, Fard A, Kottler SJ: Retrospective study of 338 canine oral melanomas with clinical, histologic, and immunohistochemical review of 129 cases. Vet Pathol 37:597-608, 2000[Abstract/Free Full Text]
  191. Ramos-Vara JA, Miller MA, Johnson GC, Turnquist SE, Kreeger JM, Watson GL: Melan A and S100 protein immunohistochemistry in feline melanomas: 48 cases. Vet Pathol 39:127-132, 2002[Abstract/Free Full Text]
  192. Reddy KP, Ramakrishna A, Reddy GCN: Malignant melanoma in a dark skinned bull. Indian Vet J 75:453-454, 1998
  193. Reddy KP, Subbaraja S: Malignant melanoma in a bullock. Indian Vet J 73:874-875, 1996
  194. Richerson JT, Burns RP, Misfeldt ML: Association of uveal melanocyte destruction in melanoma-bearing swine with large granular lymphocyte cells. Invest Ophthalmol Vis Sci 30:2455-2460, 1989[Abstract/Free Full Text]
  195. Rigel DS, Rivers JK, Kopf AW, Friedman RJ, Vinokur AF, Heilman ER, Levenstein M: Dysplastic nevi. Markers for increased risk for melanoma. Cancer 63:386-389, 1989[CrossRef][Medline]
  196. Ritt MG, Wojcieszyn J, Modiano JF: Functional loss of p21/Waf-1 in a case of benign canine multicentric melanoma. Vet Pathol 35:94-101, 1998[Abstract]
  197. Rodrigues LK, Leong SP, Ljung BM, Sagebiel RW, Burnside N, Hu TI, Ng BW, Miller JR 3rd, Kashani-Sabet M: Fine needle aspiration in the diagnosis of metastatic melanoma. J Am Acad Dermatol 42:735-740, 2000[CrossRef][Medline]
  198. Rodriguez F, Forga J, Herraez P, Andrada M, Fernandez A: Metastatic melanoma causing spinal cord compression in a horse. Vet Rec 142:248-249, 1998[Free Full Text]
  199. Roels S, Ducatelle R: Malignant melanoma of the nictitating membrane in a cat (Felis vulgaris). J Comp Pathol 119:189-193, 1998[Medline]
  200. Roels S, Tilmant K, Ducatelle R: PCNA and Ki67 proliferation markers as criteria for prediction of clinical behaviour of melanocytic tumours in cats and dogs. J Comp Pathol 121:13-24, 1999[CrossRef][Medline]
  201. Roels S, Tilmant K, Ducatelle R: P53 expression and apoptosis in melanomas of dogs and cats. Res Vet Sci 70:19-25, 2001[CrossRef][Medline]
  202. Roels S, Tilmant K, Van Daele A, Van Marck E, Ducatelle R: Proliferation, DNA ploidy, p53 overexpression and nuclear DNA fragmentation in six equine melanocytic tumours. J Vet Med A Physiol Pathol Clin Med 47:439-448, 2000[Medline]
  203. Rogers RS 3rd, Gibson LE: Mucosal, genital, and unusual clinical variants of melanoma. Mayo Clin Proc 72:362-366, 1997[Medline]
  204. Rollins SD, Berardo MD: Presence of nuclear grooves in the cytology of malignant melanoma. Diagn Cytopathol 19:309-312, 1998[CrossRef][Medline]
  205. Rudzki Z, Jothy S: CD44 and the adhesion of neoplastic cells. Mol Pathol 50:57-71, 1997[Abstract]
  206. Ryan AM, Diters RW: Clinical and pathologic features of canine ocular melanomas. J Am Vet Med Assoc 184:60-67, 1984[Medline]
  207. Saleh FH, Crotty KA, Hersey P, Menzies SW: Primary melanoma tumour regression associated with an immune response to the tumour-associated antigen melan-A/MART-1. Int J Cancer 94:551-557, 2001[CrossRef][Medline]
  208. Sanders DS, Blessing K, Hassan GA, Bruton R, Marsden JR, Jankowski J: Alterations in cadherin and catenin expression during the biological progression of melanocytic tumours. Mol Pathol 52:151-157, 1999[Abstract]
  209. Sandusky GE Jr, Carlton WW, Wightman KA: Diagnostic immunohistochemistry of canine round cell tumors. Vet Pathol 24:495-499, 1987[Abstract]
  210. Sandusky GE Jr, Carlton WW, Wightman KA: Immunohistochemical staining for S100 protein in the diagnosis of canine amelanotic melanoma. Vet Pathol 22:577-581, 1985[Abstract]
  211. Schoster JV, Dubielzig RR, Sullivan L: Choroidal melanoma in a dog. J Am Vet Med Assoc 203:89-91, 1993[Medline]
  212. Schott HC, Major MD, Grant BD, Bayly WM: Melanoma as a cause of spinal cord compression in two horses. J Am Vet Med Assoc 196:1820-1822, 1990[Medline]
  213. Scott DW: Neoplastic Diseases. In: Large Animal Dermatology, ed. Pederson D, pp 448-452, WB Saunders, Philadelphia, PA 1988
  214. Sears D, Hajdu SI: The cytologic diagnosis of malignant neoplasms in pleural and peritoneal effusions. Acta Cytol 31:85-97, 1987[Medline]
  215. Seiter S, Schadendorf D, Herrmann K, Schneider M, Rosel M, Arch R, Tilgen W, Zoller M: Expression of CD44 variant isoforms in malignant melanoma. Clin Cancer Res 2:447-456, 1996[Abstract]
  216. Shull RM, Maddux JM: Subcutaneous tissue: mammary, salivary, thyroid, and parathyroid. In: Diagnostic Cytology and Hematology of the Dog and Cat, ed. Cowell RL, Tyler RD, and Meinkoth JH, 2nd ed., pp 93-94, Mosby, St Louis, MO 1999
  217. Singh ZN, Ray R, Kumar N, Aron M, Gupta SD: Medullary thyroid carcinoma with melanin production—a case report. Indian J Pathol Microbiol 42:159-163, 1999[Medline]
  218. Slominski A, Wortsman J, Carlson AJ, Matsuoka LY, Balch CM, Mihm MC: Malignant melanoma: an update. Arch Pathol Lab Med 125:1295-1306, 2001[Medline]
  219. Sneath RJ, Mangham DC: The normal structure and function of CD44 and its role in neoplasia. Mol Pathol 51:191-200, 1998[Abstract]
  220. Stebbins KE, Morse CC, Goldschmidt MH: Feline oral neoplasia: a ten-year survey. Vet Pathol 26:121-128, 1989[Abstract]
  221. Strafuss AC, Dommert AR, Tumbleson ME, Middleton CC: Cutaneous melanoma in miniature swine. Lab Anim Care 18:165-169, 1968[Medline]
  222. Su WP: Malignant melanoma: basic approach to clinicopathologic correlation. Mayo Clin Proc 72:267-272, 1997[Medline]
  223. Suliamon S, Ehrhart E, Kitchell B: Immunohistochemical detection of canine melanomas with HMB-45. Vet Pathol 36:496, 1999
  224. Sundberg JP, Burnstein T, Page EH, Kirkham WW, Robinson FR: Neoplasms of equidae. J Am Vet Med Assoc 170:150-152, 1977[Medline]
  225. Sweeney CR, Gillette DM: Thoracic neoplasia in equids: 35 cases (1967–1987). J Am Vet Med Assoc 195:374-377, 1989[Medline]
  226. Takenouchi T, Ito K, Kazama T, Ito M: Establishment and characterization of a clear-cell sarcoma (malignant melanoma of soft parts) cell line. Arch Dermatol Res 286:254-260, 1994[CrossRef][Medline]
  227. Talley LI, Soong S, Harrison RA, McCarthy WH, Urist MM, Balch CM: Clinical outcomes of localized melanoma of the foot: a case-control study. J Clin Epidemiol 51:853-857, 1998[CrossRef][Medline]
  228. Tarrant J, Stokol T, Bartol J, Wakshlag J, Blue J: Diagnosis of malignant melanoma in a horse from cytology of body cavity fluid and blood. Equine Vet J 33:531-534, 2001[Medline]
  229. Thirloway L, Rudolph R, Leipold HW: Malignant melanomas in a Duroc boar. J Am Vet Med Assoc 130:345-347, 1977[Medline]
  230. Thompson SW: Histochemical methods for the demonstration of endogenous and exogenous pigments. In: Selected Histochemical and Histopathological Methods, pp 1284-1285, Charles C Thomas, Springfield, IL 1966
  231. Tietze MK, Chin L: Murine models of malignant melanoma. Mol Med Today 6:408-410, 2000[CrossRef][Medline]
  232. Todoroff RJ, Brodey RS: Oral and pharyngeal neoplasia in the dog: a retrospective survey of 361 cases. J Am Vet Med Assoc 175:567-571, 1979[Medline]
  233. Trosko JE: Commentary: is the concept of "tumor promotion" a useful paradigm? Mol Carcinog 30:131-137, 2001[CrossRef][Medline]
  234. Trucksa RC, McLean IW, Quinn AJ: Intraocular canine melanocytic neoplasms. J Am Anim Hosp Assoc 21:85-88, 1985