• Cause: chromatophoromas are cutaneous neoplasms arising from pigment-producing cells in reptiles (also seen in amphibians and fish). They are classified as melanophoromas, melanomas, iridophoromas, xanthophoromas, erythrophoromas or mixed, depending on the type of pigment-producing cell involved. These were once thought to be uncommon in reptiles, but melanophoromas and iridophoromas appear to show a relatively high incidence in reptiles, particularly in diurnal species. This increase in incidence is likely due to sampling bias and advancements in veterinary study of such species rather than a true increase in incidence. Most appear to have spontaneous oncogenesis, although genetic and environmental factors may play a part in their development.
• Signs: a cutaneous or subcutaneous mass or swelling, although sometimes they may present only as changes in skin pigmentation. These tumors are variable in size, may be multilobulated and can be partially encapsulated. The tumors may vary in color from orange, to red to black.
• Diagnosis: cytological or, more usually, histopathological examination will help to distinguish a chromatophoroma from other neoplastic masses or abscesses or granulomas. Immunohistochemistry and electron microscopy can help in the diagnosis of poorly pigmented or poorly differentiated neoplasms. The patient should be evaluated for signs of metastasis.
• Treatment: generally aggressive surgical excision where possible, although treatment may be unsuccessful in cases of incomplete excision, ie local recurrence, or where metastasis has occurred.
• Prognosis: good if complete excision possible but guarded if metastasis has occurred.

• A cutaneous or subcutaneous mass of swelling in a reptile. Usually these present as raised, pigmented masses, but more subtle changes in scale pigmentation have also been described. The lesions may be ulcerated.
• These can develop as single or multiple masses at various locations including the head, trunk, limbs and tail. There are a few reports of primary oral chromatophoromas, and single reports of primary pulmonary melanophoroma in a Beaded lizard, primary small intestinal chromatophoroma in a green tree python and primary iris melanoma in a gecko.
• The color of the mass may give an indication of its pigment-producing cell origin.
• May also be reported in the oral cavity.

• As above.
• Such masses appear to have a variable growth rate.
• Early skin changes in reptiles can be easily overlooked by carers, thus an apparent ‘acute’ onset of skin lesions may occasionally be reported to the clinician.

• Worldwide.

• All reported cases of chromatophoroma in reptiles occurred in adult animals.

• No sex predilection is apparent.

• Sporadic reports in the literature.
• Most frequently reported in squamates (snakes and lizards) with only a few reports in Chelonia and no reports in crocodilia or rhynchocephalia.
• In general reptile practice, Bearded dragons Bearded dragon and Veiled chameleons Veiled chameleon appear to be most commonly affected, although this apparent increase in incidence is likely due to sampling factors and advances in veterinary investigations, rather than a true increase in incidence.
• Leopard geckos (Eublepharis macularius) Leopard gecko of the ‘lemon frost’ color variant have been postulated to have a genetic predisposition to the development of cutaneous and oral iridophoromas.

• Investigation of cutaneous masses in reptiles will generally require anesthesia, biopsy of the lesion and histopathological examination at a laboratory.
• However, additional diagnostic investigations are usually required to build an adequate database to determine appropriate oncological treatments. These investigations may include hematology, serum biochemistry, urinalysis, diagnostic imaging (radiography, ultrasonography or CT), and local lymph node aspiration for cytology. Costs can therefore accumulate.
• Once a diagnosis has been confirmed, staging should be performed to check for metastasis to see whether surgical excision is feasible or indicated. Such investigations may incur significant costs.
• Costs should be discussed with the keeper prior to starting diagnostic tests and treatment.
• Radiation therapy and chemotherapy can be costly, and may only be available at tertiary veterinary centers.

• Common sites for metastasis include the regional lymph nodes, lungs, and other visceral organs.
• Pulmonary function can be compromised with lung metastases.

• Skin color in animals is determined by the amount of pigment made by pigment-producing cells within the epidermis and/or dermis:
  • In mammals and birds, melanocytes are the only type of pigment cell, whereas in reptiles, amphibians and fish, there are a variety of different cell types collectively termed chromatophores.
  • Chromatophores include iridophores, leukophores, cyanophores, xanthophores and erythrophores (the latter two often described collectively as xanthophores).
  • Melanophores, iridophores and xanthophores have been described in reptiles, and are usually located in the dermis.
• Such different pigment-producing cells give the wide variation of color in reptile skin, and the ability, in some species, to undergo rapid color change. Such adaptations help in camouflage, sexual selection and communication.
• Exact etiology of melanomas and chromatophoromas in exotic animals is currently undetermined.
• All chromatophores have the potential for neoplastic transformation:
  • Neoplasms arising from melanophores (melanin pigment-producing cells), iridophores (cells with birefringent intracytoplasmic particles that refract and reflect light), erythrophores (red-orange pigment-producing cells) and xanthophores (yellow pigment-producing cells) are collectively termed chromatophoromas.
  • Most tumors only involve one type of pigment-producing cell, although multiple pigment cell types have been involved in some tumors.
• Melanophoromas and iridophoromas are the most common types in reptiles, with fewer reports of mixed chromatophoromas, xanthophoromas and amelanotic or non-pigmented chromatophoromas.
• Generally, chromatophoromas appear to develop spontaneously and there does not appear to be a specific etiology in most cases. However, some factors do appear to play a part in the oncogenesis in some species:
  • UV radiation: there is speculation that UV radiation may contribute to the development of skin chromatophoromas in reptiles, given that many captive reptiles are exposed to artificial UV light daily, and that artificial UV radiation exposure in humans has been linked to a higher incidence of skin melanomas. This appears to be supported by the higher incidence of skin chromatophoromas in diurnal, sun-basking reptiles such as bearded dragons, and the lack of tumors found in nocturnal reptiles. Many tumors also appear to occur on the dorsal or lateral aspects of the body, and primary visceral chromatophoromas are rare. However, one review study found that neoplasms were reported in several animals that did not receive artificial UV light.
  • Genetics: a genetic predisposition to developing cutaneous and oral iridophoromas has been suggested in the ‘lemon frost’ morph of the leopard gecko Leopard gecko. A study concluded that a defect in a tumor suppressor gene, SPINT1, might be allowing neoplastic transformation of iridophores within this inbred line of leopard geckos.
  • Mutations in cancer genes: mutations have been found in the growth arrest DNA damage gene GADD34, and in the DNA mismatch repair gene MLH1 in two cases of cutaneous chromatophoroma in a jumping viper and bullsnake. It is however unclear whether the mutations were the cause of the neoplastic transformation.

General

• Chromatophoromas occur in reptiles (and amphibians and fish) but not in mammals or birds as the latter have only melanocytes as their pigment-producing cells.
• Intense and prolonged exposure to UV radiation.
• Access to excessive UV index levels in captive reptiles has been proposed as a possible etiology for chromatophoromas. Reptiles should only be exposed to appropriate species-specific UV index levels.

ℹ️Reptiles have species-specific husbandry requirements. Suboptimal or inappropriate husbandry has been implicated as the one of the most common etiologies in the pathogenesis of many diseases in captive reptiles. It is therefore important for the clinician to become familiar with the husbandry requirements of the reptile species under treatment, and make a thorough assessment of its husbandry Chelonia husbandry Lizard husbandry Snake husbandry.

• Artificial UV radiation, genetic factors and mutations of cancer genes may act as risk factors in some situations, although their true significance is currently unclear.

Specific

• Leopard geckos (Eublepharis macularius) Leopard gecko of the ‘lemon frost’ color variant have been postulated to have a genetic predisposition to the development of cutaneous and oral iridophoromas.

• See above re Etiology.
• Many chromatophoromas are deep and infiltrative masses with a high potential for metastasis.
• Many cases, particularly those reported in snakes, appear to be malignant with local invasion, local recurrence and/or distant metastases.
• There appears to be species variation in risk of metastasis and site of metastasis.
• Best described in mammals:
  • Normal melanocytes are dendritic cells derived from neuroectodermal melanoblasts. All chromatophores share a common stem cell of neural crest origin.
  • Melanocytes migrate during embryogenesis to the epidermis, dermis, and other sites.
  • In non-human mammals, most melanomas are dermal in origin. Cutaneous melanocytes are primarily confined to the hair follicles within the dermis.
  • Under normal circumstances, individual melanocytes do not form attachments with other melanocytes but instead, form adherent and regulatory junction with neighboring keratinocytes.
  • Melanin is not retained within normal melanocytes. Packaged in melanosomes and transferred through dendritic processes of melanocytes to keratinocytes.
  • Conversion of normal melanocytes (that are nonpigmented and isolated from other melanocytes) to pigmented and clustered neoplastic melanocytes is a multistep process:
    • Initiation: generation of mutation within one or more melanocytes.
    • Promotion: proliferation of mutated melanocyte(s) enables amplification of the cell population, persistence of the mutation, and opportunities for additional mutations.
    • Transformation: normal suppressors of cell proliferation and activators of apoptosis are superseded by unregulated growth factors, allowing autonomous growth.
    • Metastasis:
      • Detachment of mutated cells from the primary mass.
      • Movement to and through endothelium to travel via blood and/or lymph to a secondary site.

• Variable.
• Oncogenesis typically occurs over a long period (months to years)
• Rapid decline has been described in some reptiles (over a few weeks) after a melanophoroma diagnosis.

• Chromatophoromas occur mostly in adult reptiles, and are most frequently described in squamates with few reports in Chelonian species.

Refereed papers

• Recent references from PubMed and VetMedResource.
• Monahan C F, Garner M M & Kiupel M (2022) Chromatophoromas in reptiles. Vet Sci 9 (3) 115 PubMed.
• Pazzi P, Steenkamp G & Rixon A J (2022) Treatment of canine oral melanomas: A critical review of the literature. Vet Sci 9 (5), 196 PubMed.
• Monahan C F, Meyer A, Garner M M & Kiupe M (2021) Gross, histologic, and immunohistochemical characteristics of cutaneous chromatophoromas in captive Bearded dragons. J Vet Diag Invest 33 (5), 932-938. SageJournals.
• Muñoz-Gutiérrez J, Garner M & Kiupel M (2016) Cutaneous chromatophoromas in captive snakes. Vet Pathol 53 (6), 1213-1219 PubMed.
• Rivera S, Crane M M, McManamon R & Gregory C R (2015) Surgical treatment of pulmonary melanophoroma in a beaded lizard (Heloderma horridum exasperatum). J Zoo Wildlife Med 46 (2), 397-399 PubMed.
• Heckers K O, Aupperle H, Schmidt V & Pees M (2012) Melanophoromas and iridophoromas in reptiles. Comp Path 146 (2-3), 258-268 PubMed.
• Ha L, Noonan F P, De Fabo E C & Merlino G (2005) Animal models of melanoma. Proc J Invest Derm Symp 10 (2), 86-88 PubMed.
• Smith S , Goldschmidt M H & McManus P M (2002) A comparative review of melanocytic neoplasms. Vet Pathol 39 (6), 651-678 PubMed.

Other sources of information

• Fraser M A & Girling S J (2019) Dermatology. In: BSAVA Manual of Reptiles. 3rd edn. Eds: Girling S J & Raiti P. BSAVA, UK. pp 257-272.
• Reavill D R (2019) Neoplasia. In: BSAVA Manual of Reptiles. 3rd edn. Eds: Girling S J & Raiti P. BSAVA, UK. pp 397-410.
• Scheelings T F & Hellebuyck T (2019) Dermatology – Skin. In: Mader’s Reptile and Amphibian Medicine and Surgery. 3rd edn. Eds: Divers S J & Stahl S J. Elsevier, USA. pp 699-711.