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Melanophoromas and Iridophoromas in Reptiles
Abstract
Chromatophoromas are tumours of pigment-producing cells of the skin and are rarely reported in reptiles. These tumours are subclassified on the basis of the type of pigment. The present study characterizes chromatophoromas arising in 26 reptiles, including six snakes, 19 lizards and a tortoise. These include the first reports of melanophoromas in a yellow anaconda (Eunectes notaeus), pigmy rattlesnake (Sistrurus spp.), southern water snake (Nerodia fasciata), veiled chameleon (Chamaeleo calyptratus) and leopard gecko (Eublepharis macularius); the first reports of benign iridophoromas in a savannah monitor (Varanus exanthematicus), veiled chameleon and bearded dragon (Pogona vitticeps); and the first description of a malignant iridophoroma in a bearded dragon. Additionally, in three bearded dragons a 'mucinous' type of melanophoroma is described for the first time. Chromatophoromas generally arose from the skin of the body and head and ranged in size from 0.2 to 2.0cm in diameter. In six cases the animals were humanely destroyed immediately after diagnosis. Three further animals were humanely destroyed following recurrence of their tumour. Six of these nine reptiles had visceral metastases. Grossly, melanophoromas (n=20) were grey or black, while iridophoromas (n=6) were white in colour. Microscopically, most of the tumours were composed of spindle cells with varying pigmentation and 0-2 mitoses per 10 high power fields. Six of the 20 melanophoromas were classified as malignant due to the presence of intravascular tumour cells, visceral metastases, high pleomorphism and/or mitotic figures. Five of the six iridophoromas were classified as benign and the one malignant tumour was defined by the presence of intravascular tumour cells and visceral metastases. Immunohistochemically, melan A and S100 were coexpressed by all of the chromatophoromas.
... musculature through connective tissue. The chromatophores present in the dermis are a group of cells histologically analogous to melanocytes in mammals, containing pigments and light reflectors inside and are divided into melanophores, xanthophores, iridophores and erythrophores (1,2). ...
... Chromatophoromas, in general, can have a malignant behavior, which highlights the importance of careful postoperative monitoring, in addition to being extremely important to remove the tumor with free margins, as carried out in the present study (2). According to a retrospective study by Kubiak (6), the most common skin neoplasm in lacertids is squamous cell carcinoma, and melanophoroma is in seventh place, with a 3.9% rate of incidence. ...
... According to a retrospective study by Kubiak (6), the most common skin neoplasm in lacertids is squamous cell carcinoma, and melanophoroma is in seventh place, with a 3.9% rate of incidence. In the study by Hackers (2), which specified only tumors originating from chromatophores, melanophoroma was the most common. Although it has not been reported in Salvator merianae, the most affected species was a lacertidae, Pogona vitticeps. ...
Cutaneous neoplasms have been described in the class Reptilia, and many of them are related to the inadequate management of these animals in captivity. In Brazil, there are few reports of cutaneous neoplasms in Iguana iguana, but no reported cases in Salvator merianae. Therefore, the objective of this work was to report a case of a melanophoroma diagnosed in a Salvator merianae. A tegu with a skin nodule located in the dorsal region, close to the right scapula, measuring 1 cm, in diameter, blackish, elevated, firm in consistency, well defined, non-ulcerated and non-adherent, was surgically removed and sent to histopathology analysis, witch revel melanophoroma. The animal in this report had a follow up for eight months after the procedure, and was discharged without signs of other skin nodules. The present report seeks to add to the literature on reptile medicine by describing a histopathological diagnosis of melanophoroma in Salvator merianae, in addition to the clinical-surgical treatment and its respective clinical follow-up.
... Based on animals sent to diagnostic pathology services, the incidence of neoplasia in reptiles ranges from 12% to 26% [1][2][3][4]. Variation in these estimates may be due to reporting bias based on differences in location, type of collection, and private studies conducting verification. Turtles and tortoises have a relatively low incidence of neoplasia (10.3%) [1,2,5]. ...
... The haematopoietic and lymphoid systems are most affected, followed by neoplasms of epithelial origin [9,10], of which renal adenomas and adenocarcinomas appear to have a high incidence. Among skin tumours, melanophoroma is the third most common type of tumour reported in snakes, usually presenting as a single skin mass [4,11]. Among the adenomas and renal adenocarcinomas examined in eight snakes, most tumours were characterised by a low mitotic index and a locally invasive nature [12]. ...
... Melanophoromas are the third most common type of tumour reported in snakes, usually presenting as a single skin mass. These tumours are locally invasive and have a poor prognosis [4,11,13]. Ovarian adenocarcinomas have been described in several snake species and are typically associated with diffuse metastases and a poor prognosis. These tumours may have a hormonal predisposition, although the cause has not been established [14]. ...
Simple Summary
An adult male variable kingsnake was examined for a three-week history of anorexia and body deformities, revealing poor condition and an intracoelomic mass. With the owner’s consent, an exploratory celiotomy was performed to remove the mass, which was identified as an undifferentiated tumour by modified Wright–Giemsa stain smears. Histological examination revealed a solid proliferation of highly tubular anaplastic cells and plurinucleated cells positive for cytokeratin and vascular endothelial growth factor, but not vimentin. Periodic acid–Schiff staining showed large granular cells characteristic of efferent ducts. A diagnosis of extratesticular anaplastic carcinoma was made as the first reported case in the male genital apparatus of snakes.
Abstract
An adult male variable kingsnake (Lampropeltis mexicana) was presented for examination due to a three-week history of anorexia and obvious body deformities. On objective examination the animal was in poor condition, and on palpation, an intracoelomic mass was noted approximately in the distal third of the body, cranial to the cloaca. In agreement with the owner, an exploratory celiotomy was planned and performed and the mass was surgically removed. Modified Wright–Giemsa stain impression smears were taken, which were consistent with an undifferentiated tumour. Histological examination revealed the presence of a solid proliferation composed of highly tubular anaplastic cells and abundant multinucleated cells. The neoplastic cells were positive for cytokeratin (AE1/AE3), but not for vimentin. Periodic acid–Schiff (PAS) staining revealed the presence of large granular cells, which can be identified as the characteristic cells of the efferent ducts. Based on the morphological and immunohistochemical findings, the diagnosis of extratesticular anaplastic carcinoma was made. To the authors’ knowledge, this type of neoplasm has never been reported in the male genital apparatus of snakes.
... Melanophoromas and iridophoromas are most common, with few reports of mixed chromatophoromas, xanthophoromas, and amelanotic or non-pigmented chromatophoromas [8,[11][12][13]17,18]. Of the different reptilian orders, they are most frequently described in squamata with few reports in testudines (chelonia) and no reports in crocodilia or rhynchocephalia [9,[11][12][13][14][19][20][21] Affected animals are almost always adults and no sex predilection is apparent [9,[11][12][13][14]. Most reports are cutaneous chromatophoromas that develop as single or multiple masses at various sites, including the head, trunk, limbs (when applicable), and tail [9,12,13,22,23]. ...
... Melanophoromas and iridophoromas are most common, with few reports of mixed chromatophoromas, xanthophoromas, and amelanotic or non-pigmented chromatophoromas [8,[11][12][13]17,18]. Of the different reptilian orders, they are most frequently described in squamata with few reports in testudines (chelonia) and no reports in crocodilia or rhynchocephalia [9,[11][12][13][14][19][20][21] Affected animals are almost always adults and no sex predilection is apparent [9,[11][12][13][14]. Most reports are cutaneous chromatophoromas that develop as single or multiple masses at various sites, including the head, trunk, limbs (when applicable), and tail [9,12,13,22,23]. ...
... Of the different reptilian orders, they are most frequently described in squamata with few reports in testudines (chelonia) and no reports in crocodilia or rhynchocephalia [9,[11][12][13][14][19][20][21] Affected animals are almost always adults and no sex predilection is apparent [9,[11][12][13][14]. Most reports are cutaneous chromatophoromas that develop as single or multiple masses at various sites, including the head, trunk, limbs (when applicable), and tail [9,12,13,22,23]. Chromatophoromas most often present as raised, pigmented masses, but more subtle alterations in scale pigmentation are less commonly described [9,[12][13][14] (Figure 1a-e). ...
Chromatophoromas are neoplasms that arise from pigment cells of reptiles, amphibians, and fish. They include melanophoromas (melanomas), iridophoromas, and xanthophoromas. Most chromatophoromas develop spontaneously, but genetic and environmental factors may also play a role in their oncogenesis. The diagnosis is typically through histologic examination. Immunohistochemistry and electron microscopy can be helpful for diagnosing poorly differentiated and/or poorly pigmented neoplasms. Aggressive surgical excision is the current treatment of choice. This review describes the clinical presentation, gross appearance, diagnostic applications, clinical behavior, and treatment of chromatophoromas in reptiles.
... To characterize the origin of the neoplasm, immunohistochemistry (IHC) was carried out using a panel of anti-human and anti-bovine antibodies ( Table 1). The antibodies against melan-A and S100 have been demonstrated to cross-react with the respective antigens in reptiles (Kusewitt et al, 1997;Irizarry-Rovira et al, 2006;Heckers et al, 2012). Sections were labelled using a Fully Automated Immunohistochemistry Stainer (Leica Biosystems, Newcastle, UK) according to the manufacturer's instructions. ...
... Furthermore, PEComas and melanophoromas exhibit differences in location and histological features. While most primary melanophoromas commonly occur in the integument and occasionally in the oral cavity of reptiles (Irizarry-Rovira et al, 2006;Heckers et al, 2012), the colon, which was the most likely origin of the neoplasm in this case, is one of the common locations for PEComas. Furthermore, the unusual finding of perivascular epithelioid cells with an inherent tendency to bulge into vascular lumina is absent in melanophoromas (Heckers et al, 2012). ...
... While most primary melanophoromas commonly occur in the integument and occasionally in the oral cavity of reptiles (Irizarry-Rovira et al, 2006;Heckers et al, 2012), the colon, which was the most likely origin of the neoplasm in this case, is one of the common locations for PEComas. Furthermore, the unusual finding of perivascular epithelioid cells with an inherent tendency to bulge into vascular lumina is absent in melanophoromas (Heckers et al, 2012). Collectively, the gross, histopathological and IHC findings in this case support a diagnosis of malignant PEComa, which, to the best of our knowledge, is the first report of PEComa in any non-human species. ...
A 9-year-old male captive savannah monitor (Varanus exanthematicus) with a history of general debility was submitted for necropsy. Grossly, there were multiple white masses in the colon, mesorchium and tracheal adventitia. Histologically, the lesions were composed of epithelioid to spindloid neoplastic cells arranged in sheets to interlacing and interwoven bundles, and separated by abundant myxoid material or extensive stromal hyalinization and fibrosis with occasional chondroid metaplasia. Perivascular infiltration of epithelioid neoplastic cells was occasionally seen. Neoplastic cells were immunopositive for alpha-smooth muscle actin, melan-A and S100. The unique histological features and concurrent myogenic and melanocytic immunophenotypes suggest a malignant perivascular epithelioid cell tumour. To our knowledge, this is the first report of perivascular epithelioid cell tumours in a non-human species.
... Paraffinembedded tissues were sectioned at 5 µm, mounted on frosted glass slides, and stained with hematoxylin and eosin (H&E). Periodic acid-Schiff (PAS) stain (cases 5,6,10,11,13,15,17) was also applied for mucinous tumors. Some heavily pigmented tumors were bleached with 10% H 2 O 2 (cases 13,15). ...
... This low prevalence is in agreement with most of the reports in bearded dragons, 5,14 although one study reported a higher prevalence, perhaps because the relative prevalence was compared to other reptile species with chromatophoromas in their study, rather than to the total number of bearded dragon submissions to their laboratory. 10 Also, all of those animals were privately owned, 10 hence differences in husbandry, genetics, or environment could have played a role. ...
... 1 As described in other reports of chromatophoromas in bearded dragons, a subset of the neoplasms in our series was associated with PAS-positive, mucinous stroma. 10 This variant was not correlated with a specific subset, although one of these neoplasms also had osseous and cartilaginous metaplasia, which has not been described in other reports in bearded dragons but has been described rarely in human and canine melanomas. 2,3,17,25,32 In all of the cases in our series, metastasis was not noted at the time of excision, and lymphatic invasion was not observed. ...
Chromatophoromas are neoplasms that develop from the dermal pigment-bearing and light-reflecting cells (chromatophores) in the skin of reptiles, fish, and amphibians. Seventeen cutaneous chromatophoromas were identified from 851 bearded dragon submissions (2%) to a private diagnostic laboratory in a 15-y period. No sex predilection was found. Ages ranged from 9 mo to 11 y. Chromatophoromas most commonly were single, raised, variably pigmented masses or pigmented scales on the trunk, and less commonly the extremities or head. Microscopically, iridophoromas, melanophoromas, mixed chromatophoromas, and nonpigmented chromatophoromas were identified. Neoplasms were often ulcerated and invaded deep into the subcutis and muscle. Most commonly, nuclear atypia was mild-to-moderate, and mitotic count was low. Six neoplasms had abundant, periodic acid-Schiff-positive, mucinous stroma. Histologic examination was often adequate to diagnose chromatophoromas in bearded dragons given that 11 of 17 had some degree of pigmentation, although it was often scant. IHC for S100 and PNL2 could be helpful to diagnose poorly pigmented neoplasms. No lymphatic invasion or metastases at the time of excision were noted in any of the cases. Follow-up data were available for 6 cases, with no reports of recurrence or neoplasia-related death. Two cases had elevated mitotic counts and nuclear pleomorphism, which has been associated with metastasis in other reports of bearded dragon chromatophoromas. In general, it appears that aggressive surgical excision is often curative, but monitoring may be warranted for cases in which tumors had high mitotic count and nuclear pleomorphism.
... Lemon Frost is characterized by an increased white body colouration and a brightening of the yellow/orange areas of the body (SZYDLOWSKI et al., 2020). The breeders observed soon that large number of Lemon Frost leopard geckos were affected by numerous tumour-like skin lesions, especially chromatophoromas (diagnosed as iridophoromas) (HECKERS et al., 2012;SZYDLOWSKI et al., 2020). Although most of reptile skin neoplasms exhibit locally aggressive behaviour, they show a relatively low incidence to metastasize (HELLEBUYCK et al., 2012). ...
... Iridophoromas are pigment-producing cells tumours that have been reported in different reptile species (HECKERS et al., 2012;HELLEBUYCK et al., 2012;MUNOZ-GUTIÉRREZ et al., 2016;GUO ROUSSELET et al., 2017;SZYDLOWSKI et al., 2020). Iridophoroma has spindle-shaped cell morphology, invasive growth and marked pigmentation. ...
... Iridophoroma has spindle-shaped cell morphology, invasive growth and marked pigmentation. Iridophoromas have been reported as the skin lesions only or skin lesions with the visceral metastases (SZYDLOWSKI et al., 2020;HECKERS et al., 2012). Metastatic and malignant iridophoromas have been described in snakes (JACOBSON et al., 1989;HECKERS et al., 2012). ...
At the time of birth, newborn llamas and alpacas present in the anterior longitudinal presentation and dorso-sacral position with the head resting on the metacarpal bones of the extended forelegs. The newborn (called a cria) stands very soon to suckle colostrum within the first 2 hours, and may suckle up to 10 times per day during the first seven days of life. Colostrum is only available for 3-4 days, but immunoglobulin absorption occurs only during the first 24 hours of life. Milk production reaches its peak by 2-3 weeks of lactation and then declines by the first month of lactation. Preweaning mortality is 20-80 % in South America, as opposed to 2-5 % in developed countries. The most common diagnoses of neonatal llamas and alpacas are systemic inflammations, congenital defects, sepsis, gastrointestinal diseases, and others.
... Lemon Frost is characterized by an increased white body colouration and a brightening of the yellow/orange areas of the body (SZYDLOWSKI et al., 2020). The breeders observed soon that large number of Lemon Frost leopard geckos were affected by numerous tumour-like skin lesions, especially chromatophoromas (diagnosed as iridophoromas) (HECKERS et al., 2012;SZYDLOWSKI et al., 2020). Although most of reptile skin neoplasms exhibit locally aggressive behaviour, they show a relatively low incidence to metastasize (HELLEBUYCK et al., 2012). ...
... Iridophoromas are pigment-producing cells tumours that have been reported in different reptile species (HECKERS et al., 2012;HELLEBUYCK et al., 2012;MUNOZ-GUTIÉRREZ et al., 2016;GUO ROUSSELET et al., 2017;SZYDLOWSKI et al., 2020). Iridophoroma has spindle-shaped cell morphology, invasive growth and marked pigmentation. ...
... Iridophoroma has spindle-shaped cell morphology, invasive growth and marked pigmentation. Iridophoromas have been reported as the skin lesions only or skin lesions with the visceral metastases (SZYDLOWSKI et al., 2020;HECKERS et al., 2012). Metastatic and malignant iridophoromas have been described in snakes (JACOBSON et al., 1989;HECKERS et al., 2012). ...
At the time of birth, newborn llamas and alpacas present in the anterior longitudinal presentation and dorso-sacral position with the head resting on the metacarpal bones of the extended forelegs. The newborn (called a cria) stands very soon to suckle colostrum within the first 2 hours, and may suckle up to 10 times per day during the first seven days of life. Colostrum is only available for 3-4 days, but immunoglobulin absorption occurs only during the first 24 hours of life. Milk production reaches its peak by 2-3 weeks of lactation and then declines by the first month of lactation. Preweaning mortality is 20-80 % in South America, as opposed to 2-5 % in developed countries. The most common diagnoses of neonatal llamas and alpacas are systemic inflammations, congenital defects, sepsis, gastrointestinal diseases, and others.
... In reptiles, these cells include melanophores (producing black melanins), iridophores (producing birefringent, variably coloured purine crystals) and xanthophores (producing red, orange or yellow carotenoid and pteridine pigments) (Bagnara et al, 1968). Chromatophoromas are tumours arising from these pigmented cells in general and are more specifically termed melanophoromas (melanomas), iridophoromas or xanthophoromas (Heckers et al, 2012). Mixed chromatophoromas have also been reported, as have benign and malignant tumour variants (Jacobson et al, 1989;Gregory et al, 1997;Muñoz-Guti errez et al, 2016). ...
... Mixed chromatophoromas have also been reported, as have benign and malignant tumour variants (Jacobson et al, 1989;Gregory et al, 1997;Muñoz-Guti errez et al, 2016). Until recently, there have been only rare case reports of the clinicopathological features of chromatophoromas in snakes, lizards and tortoises (Heckers et al, 2012). A North American retrospective review of 42 chromatophoromas in captive snakes has subsequently found colubrids to be the most commonly affected species (55%), followed by vipers (19%), boids (17%) and pythons (7%), with only a single case described in an elapid (a Cape cobra, which is a Southern African elapid species) (Muñoz-Guti errez et al, 2016). ...
... A North American retrospective review of 42 chromatophoromas in captive snakes has subsequently found colubrids to be the most commonly affected species (55%), followed by vipers (19%), boids (17%) and pythons (7%), with only a single case described in an elapid (a Cape cobra, which is a Southern African elapid species) (Muñoz-Guti errez et al, 2016). In Australian reptiles, the few reports of chromatophoromas include multiple examples of melanophoromas and iridophoromas in the central bearded dragon (Pogona vitticeps) (Heckers et al, 2012), iridophoromas in a dwarf bearded dragon (Pogona henrylawsoni) (de Brot et al, 2015) and a green tree python (Morelia viridis) and melanophoromas in a woma (Aspidites ramsayi) and a carpet python (Morelia spilota) (Muñoz-Guti errez et al, 2016). The current report documents the clinicopathological features of chromatophoromas in four species of Australian elapid. ...
This report documents the clinicopathological features of cutaneous chromatophoromas in four wild-caught, captive Australian elapid snakes: a strap-snouted brown snake (Pseudonaja aspidoryncha), a tiger snake (Notechis scutatus), an Eastern brown snake (Pseudonaja textilis) and a Mengden's brown snake (Pseudonaja mengdeni). All tumours were subclassified as melanophoromas, with three assessed as malignant on the basis of invasive growth or presence of intracoelomic metastases. The chromatophoromas were single or multiple, black or orange pigmented, cutaneous, sometimes ulcerated, plaques or nodules. Microscopically, the neoplastic cells were often spindle shaped with low or variable pigmentation. Neoplastic cells in one tumour were notable for their pleomorphic round cell morphology and high mitotic rate. One snake with late-stage metastasis survived for over 5 years. There are few reports of chromatophoromas in elapid snakes and, to our knowledge, this is the first report of these tumours in Australian elapid snakes.
... In reptiles, tumours of pigment-producing cells of the skin are called chromatophoromas and are subclassified on the basis of the type of pigment, specifically melanophoromas or iridophoromas. A review of chromatophoromas that arose in 26 reptiles (6 snakes, 19 lizards, and 1 tortoise) found that six of the 20 melanophoromas were classified as malignant, due to the presence of intravascular tumour cells, visceral metastases, high pleomorphism, and/or mitotic figures [43]. Microscopically, most of the tumours were composed of spindle cells with varying pigmentation, and both melan A and S100 were expressed by all of the tumours by immunohistochemistry [43]. ...
... A review of chromatophoromas that arose in 26 reptiles (6 snakes, 19 lizards, and 1 tortoise) found that six of the 20 melanophoromas were classified as malignant, due to the presence of intravascular tumour cells, visceral metastases, high pleomorphism, and/or mitotic figures [43]. Microscopically, most of the tumours were composed of spindle cells with varying pigmentation, and both melan A and S100 were expressed by all of the tumours by immunohistochemistry [43]. Six of the nine reptiles that were euthanised immediately after diagnosis or following tumour recurrence had visceral metastases [43]. ...
... Microscopically, most of the tumours were composed of spindle cells with varying pigmentation, and both melan A and S100 were expressed by all of the tumours by immunohistochemistry [43]. Six of the nine reptiles that were euthanised immediately after diagnosis or following tumour recurrence had visceral metastases [43]. Figure 2 shows a metastatic melanophoroma found at autopsy of a 60-year old red-eared slider turtle (Trachemys scripta elegans). ...
In contrast to other cancer types, melanoma incidence has been increasing over the last 50 years, and while it still represents less than 5% of all cutaneous malignancies, melanoma accounts for the majority of skin cancer deaths, due to its propensity to metastasise. Whilst melanoma most commonly affects the skin, it can also arise in mucosal surfaces, the eye and the brain. For new therapies to be developed, a better understanding of the genetic landscape, signalling pathways and tumour‐microenvironmental interactions are needed. This is where animal models are of critical importance. The mouse is the foremost used model of human melanoma. Arguably this is due to its plethora of benefits as a laboratory animal, however, it is important to note that unlike humans, melanocytes are not present at the dermal‐epidermal junction in mice and mice do not develop melanoma without genetic manipulation. In contrast, there are numerous reports of animals that spontaneously develop melanoma, ranging from sharks and parrots to hippos and monkeys. In addition, several domesticated and laboratory‐bred animals spontaneously develop melanoma or UV‐induced melanoma, specifically, fish, opossums, pigs, horses, cats and dogs. In this review, we look at spontaneously occurring animal ‘models’ of melanoma and discuss their relevance to the different types of melanoma found in humans.
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... In de dermis van reptielen kunnen vier verschillende types pigmentcellen of chromatoforen voorkomen; melanoforen (melanine-producerende cellen), xantoforen (carotenoïd-producerende cellen), erytroforen (pteridine-producerende cellen) en iridoforen (kristallijn purine-producerende cellen die reflecterende granulen bevatten bestaande uit guanine, adenine, hypoxanthine of urinezuur) (Bagnara et al., 1968;1979;Heckers et al., 2012;Muñoz-Gutiérrez et al., 2016). Deze cellen ontstaan net als de melanocyten bij zoogdieren in de neurale lijst van het embryo (Hadley en Goldman, 1969, Bagnara et al., 1979Teyssier et al., 2015;Schartl et al., 2016). ...
... Deze kunnen van elkaar onderscheiden worden door de celvorm en hun vermogen tot aggregatie of verstrooiing van hun reflecterende organellen, wat uiteindelijk resulteert in de verschillende kleurschakeringen die ze genereren. Iridoforen bezitten intracytoplasmatische partikels die licht refracteren en reflecteren, waardoor deze cellen in staat zijn om blauwe, witte en ultraviolette kleurtinten te genereren wanneer ze belicht worden, terwijl via leukoforen een verbleking van de huidkleuren verkregen wordt (Bagnara et al., 1968;1979;Heckers et al., 2012;de Brot et al., 2015;Teyssier et al., 2015;Schartl et al., 2016). Lichtabsorberende pigmentcellen worden onderverdeeld in xantoforen, erytroforen en cyanoforen die respectievelijk geel, rood en blauw kleuren. ...
... Neoplasieën van chromatoforen worden met een gemeenschappelijke term benoemd als chromatoforoma's en werden reeds beschreven bij vissen, reptielen en amfibieën (Schmidt-Posthaus et al., 2005;Camus et al., 2011;Martínez-Silvestre et al., 2011;Heckers et al., 2012;Muñoz-Gutiérrez et al., 2016;Schartl et al., 2016;Singaravel et al., 2016). In tegenstelling tot wat oorspronkelijk verondersteld werd, blijken chromatoforoma's relatief vaak voor te komen bij in gevangenschap gehouden reptielen, in het bijzonder bij dagactieve soorten die blootgesteld worden aan artificieel ultraviolet (UV) licht (Heckers et al., 2012;Heckers en Aupperle, 2014;Bielli et al., 2015;Lewis et al., 2015;Rivera et al., 2015). ...
Neoplasieën van de pigmentcellen of chromatoforen bij reptielen worden naargelang hun oorsprong geclassificeerd als melanoforoma’s, iridoforoma’s, xantoforoma’s, erytroforoma’s of gemengde chromatoforoma’s. In tegenstelling tot wat oorspronkelijk verondersteld werd, komen deze primaire, cutane neoplasieën regelmatig voor bij in gevangenschap gehouden reptielen. Melanoforoma’s en iridoforoma’s worden het meest frequent vastgesteld. Een definitieve diagnose van chromatoforoma’s wordt bekomen door middel van histologisch onderzoek. Aanvullend is immunohistochemie of elektronenmicroscopie soms noodzakelijk om chromatoforoma’s onderling te differentiëren. Complete chirurgische excisie wordt beschouwd als de voorkeursbehandeling. Vanwege de uitgesproken maligniteit en neiging tot metastasering is de prognose van chromatoforoma’s bij reptielen over het algemeen echter sterk gereserveerd. Een vroegtijdige en correcte diagnose van deze neoplastische aandoening bij reptielen is daarom van primordiaal belang. In dit artikel wordt een overzicht gegeven van de huidige kennis omtrent het voorkomen, het biologisch gedrag, de pathogenese en de diagnostische en therapeutische benadering van chromatoforoma’s bij reptielen met de nadruk op melano- en iridoforoma’s.
... In veterinary practice, reptile neoplasms affecting any kind of tissue or organ are not frequently observed 11 , and skin tumours seem to be particularly rare. The frequency of chromatophoromas in reptiles is estimated at 14.5%, and melanophoromas (11.2%) are more often encountered than iridophoromas (3.3%) 12 . Melanophoromas have been reported in several cases [11][12][13] . ...
... The frequency of chromatophoromas in reptiles is estimated at 14.5%, and melanophoromas (11.2%) are more often encountered than iridophoromas (3.3%) 12 . Melanophoromas have been reported in several cases [11][12][13] . Iridophoromas have been found in a few cases, e.g in Pituophis melanoleucus and Morelia viridis 14 . ...
... much evidence that iridophoromas in reptiles may be either benign or malignant. Benign iridophoromas have been reported in veiled chameleon (Chamaeleo calyptratus), a bearded dragons (Pogona vitticeps), and a savannah monitor (Varanus exanthematicus) 12 . Cases of malignant iridophoromas were found in snakes 14,15 , in a dwarf bearded dragon (Pogona henrylawsoni) 16 and in green iguana (Iguana iguana) 17 . ...
The Lemon Frost is a new colour morph of the leopard gecko, which emerged in ca. 2015 as a result of selective breeding and spontaneous mutation. According to multiple breeders observation of Lemon Frost inbreeding with wild-type leopard geckos, Lemon Frost seems to be a codominant trait. Additionally breeders observed another, presumably associated trait - tumour-like skin lesions. Three private-owned Lemon Frost morph leopard geckos with tumour-like skin lesions were admitted to our clinic for examination, which included histopathology, X-ray and ultrasonography. The histopathological investigation of the biopsies indicated malignant iridophoroma; however, no changes were observed in diagnostic imaging. This research is the first report of clinical and histopathological findings of iridophoroma in leopard geckos.
... 6 There have been few reports of chromatophoromas in reptiles, and these are limited to lizards and snakes only. [7][8][9][10][11][12][13][14] Within these reports of chromatophoromas in reptiles, there are significantly fewer publications specifically describing iridophoromas. 2,4,9,11,12 In lizard species, benign iridophoromas have been reported in central bearded dragons (Pogona vitticeps), a Lawson's dragon (Pogona henrylawsoni), a veiled chameleon (Chamaeleo calyptratus), and a savannah monitor (Varanus exanthematicus). ...
... [7][8][9][10][11][12][13][14] Within these reports of chromatophoromas in reptiles, there are significantly fewer publications specifically describing iridophoromas. 2,4,9,11,12 In lizard species, benign iridophoromas have been reported in central bearded dragons (Pogona vitticeps), a Lawson's dragon (Pogona henrylawsoni), a veiled chameleon (Chamaeleo calyptratus), and a savannah monitor (Varanus exanthematicus). 4,9 Malignant iridophoromas have been reported in a Lawson's dragon, 4 a bearded dragon, 9 and a veiled chameleon. ...
... 2,4,9,11,12 In lizard species, benign iridophoromas have been reported in central bearded dragons (Pogona vitticeps), a Lawson's dragon (Pogona henrylawsoni), a veiled chameleon (Chamaeleo calyptratus), and a savannah monitor (Varanus exanthematicus). 4,9 Malignant iridophoromas have been reported in a Lawson's dragon, 4 a bearded dragon, 9 and a veiled chameleon. 2 This report examines the diagnostic, clinical, and pathological features of metastasizing iridophoroma in 2 lizard species from the same zoological collection. ...
Iridophores are iridescent cutaneous pigment cells found in reptiles, fish, and amphibians. Neoplasms of iridophores are rarely reported, and little is known about their behaviour, metastatic potential, and prognostic indicators. This paper reports details of the clinical course and pathological findings of metastatic iridophoroma in a veiled chameleon (Chamaeleo calyptratus) and red-barred dragon (Ctenophorus vadnappa). The veiled chameleon presented with a subcutaneous mass on the right lateral elbow and was diagnosed as an iridophoroma on fine needle aspiration. It was otherwise clinically normal. Within 35 days of excision, multiple secondary skin masses developed which were often non-pigmented and required microscopic examination to identify them as iridophoroma metastases. There were in total 54 days between the first detection of the primary mass and end stage, extensive cutaneous and visceral metastatic disease, and there had been no detectable primary mass during routine clinical examination 128 days prior to death. The red-barred dragon presented with a white sub-mandibular mass. While undergoing an excisional biopsy the animal expired, post-mortem examination revealed a cutaneous malignant iridophoroma with tumour cell clusters seen in pulmonary arterial vessels, suggesting that surgical handling of iridophoroma could precipitate the release of circulating tumour cell clusters. This is the first iridophoroma described in a red-barred dragon and the second report of a malignant iridophoroma in a veiled chameleon. Timely detection and careful excision of lizard iridophoroma may be an important factor in clinical outcome.
... 5 In lizards, melanophoromas represented 13.7% of tumors, followed by iridophoromas (6.3%). 6 Most melanophoromas appear darker than iridophoromas, which are typically single white intradermal nodules. 6 Iridophoromas are tumors composed of cells with intracytoplasmic crystalline purine material that is reflective or iridescent and birefringent when exposed to polarized light. ...
... 6 Most melanophoromas appear darker than iridophoromas, which are typically single white intradermal nodules. 6 Iridophoromas are tumors composed of cells with intracytoplasmic crystalline purine material that is reflective or iridescent and birefringent when exposed to polarized light. 6 Iridophoromas may be either benign or malignant. ...
... 6 Iridophoromas are tumors composed of cells with intracytoplasmic crystalline purine material that is reflective or iridescent and birefringent when exposed to polarized light. 6 Iridophoromas may be either benign or malignant. Benign iridophoromas have been reported in Bearded dragons (Pogona vitticeps), a Veiled chameleon (Chamaeleo calyptratus), and a Savannah monitor (Varanus exanthematicus). ...
An 11-year-old intact male Green iguana (Iguana iguana) was referred for treatment of a probable iridophoroma based on previous cytopathology. A periocular mass was present near the right medial canthus. Computed tomography did not show any sign of metastasis. Clinicopathologic abnormalities included lymphopenia and hyperproteinemia. Cytologic and histologic evaluations of the mass were consistent with iridophoroma. Complete surgical excision of the mass was not possible without removal of the orbit due to local tissue involvement. Recovery and suture removal were unremarkable. Adjunctive radiation therapy was recommended, but not performed. A year later, the surgical site had healed well. To our knowledge, this is the first reported chromatophoroma cytopathology in a Green iguana. Chromatophoromas should be included in the differential diagnoses of pigmented skin tumors in reptiles. Early surgical excision is useful to limit local tissue destruction and metastatic potential.
... In de dermis van reptielen kunnen vier verschillende types pigmentcellen of chromatoforen voorkomen; melanoforen (melanine-producerende cellen), xantoforen (carotenoïd-producerende cellen), erytroforen (pteridine-producerende cellen) en iridoforen (kristallijn purine-producerende cellen die reflecterende granulen bevatten bestaande uit guanine, adenine, hypoxanthine of urinezuur) (Bagnara et al., 1968;1979;Heckers et al., 2012;Muñoz-Gutiérrez et al., 2016). Deze cellen ontstaan net als de melanocyten bij zoogdieren in de neurale lijst van het embryo (Hadley en Goldman, 1969, Bagnara et al., 1979Teyssier et al., 2015;Schartl et al., 2016). ...
... Deze kunnen van elkaar onderscheiden worden door de celvorm en hun vermogen tot aggregatie of verstrooiing van hun reflecterende organellen, wat uiteindelijk resulteert in de verschillende kleurschakeringen die ze genereren. Iridoforen bezitten intracytoplasmatische partikels die licht refracteren en reflecteren, waardoor deze cellen in staat zijn om blauwe, witte en ultraviolette kleurtinten te genereren wanneer ze belicht worden, terwijl via leukoforen een verbleking van de huidkleuren verkregen wordt (Bagnara et al., 1968;1979;Heckers et al., 2012;de Brot et al., 2015;Teyssier et al., 2015;Schartl et al., 2016). Lichtabsorberende pigmentcellen worden onderverdeeld in xantoforen, erytroforen en cyanoforen die respectievelijk geel, rood en blauw kleuren. ...
... Neoplasieën van chromatoforen worden met een gemeenschappelijke term benoemd als chromatoforoma's en werden reeds beschreven bij vissen, reptielen en amfibieën (Schmidt-Posthaus et al., 2005;Camus et al., 2011;Martínez-Silvestre et al., 2011;Heckers et al., 2012;Muñoz-Gutiérrez et al., 2016;Schartl et al., 2016;Singaravel et al., 2016). In tegenstelling tot wat oorspronkelijk verondersteld werd, blijken chromatoforoma's relatief vaak voor te komen bij in gevangenschap gehouden reptielen, in het bijzonder bij dagactieve soorten die blootgesteld worden aan artificieel ultraviolet (UV) licht (Heckers et al., 2012;Heckers en Aupperle, 2014;Bielli et al., 2015;Lewis et al., 2015;Rivera et al., 2015). ...
Tumors of the pigment cells or chromatophores in reptiles are classified as melanophoromas, iridophoromas, xanthophoromas, erythrophoromas or mixed type chromatophoromas based on the predominant type of pigment, and constitute a relatively common neoplastic disorder in captive reptiles. Especially melanophoromas and iridophoromas are frequently observed. The diagnosis of chromatophoromas is usually made through histological examination. The use of immunohistochemistry or electron microscopy may be required to discriminate the different types of chromatophoromas. Whenever possible, complete surgical excision is the treatment of choice. Due to the distinct malignancy and tendency to metastasize, the prognosis of cutaneous chromatophoromas in reptiles is generally guarded. Consequently, an early and correct diagnosis of these neoplastic disorders in reptiles is vital. This article provides an overview of the current knowledge regarding the occurrence, the performance, the pathogenesis and the diagnostic and therapeutic approach of chromatophoromas in reptiles with emphasis on melano- and iridophoromas.
... 5 Recently, advances in medical knowledge and diagnostic capabilities in veterinary medicine have improved antemortem diagnostics and neoplasia is now a more commonly diagnosed clinical problem affecting a wide variety of reptilian species. [2][3][4][6][7][8][9][10] Reptiles are becoming increasingly popular in the United States as pets, 11 and continue to be maintained in zoologic and research settings. Modern reptile owners are more likely to be interested in pursuing advanced diagnostics and treatments. ...
... These tumors of pigment producing cells are locally invasive and have a poor prognosis for the affected snake. 10,24,48 A retrospective study of chromatophoromas in snakes, lizards, and a tortoise showed a higher rate of malignancy for melanophoromas than iridiophoromas. A mucinous subtype of melanophoromas, characterized by a proteoglycan-rich extracellular matrix, described in bearded dragons, a Hermann's tortoise, and a red-bellied cooter, also has a poor prognosis based on local invasion rather than metastasis. ...
... A mucinous subtype of melanophoromas, characterized by a proteoglycan-rich extracellular matrix, described in bearded dragons, a Hermann's tortoise, and a red-bellied cooter, also has a poor prognosis based on local invasion rather than metastasis. 10,33,51,58 Definitive diagnosis and differentiation of chromatophoromas can be attempted with immunohistochemistry. Ovarian adenocarcinomas have been described in several snake species, and typically involve widespread metastasis and a poor prognosis. These tumors may have a hormonal predisposition, although causality has not been established. ...
Based on necropsy review, neoplasia in reptiles has a comparable frequency to that of mammals and birds. Reptile neoplasia is now more frequently diagnosed in clinical practice based on increased use of advanced diagnostic techniques and improvements in reptilian husbandry allowing greater longevity of these species. This article reviews the current literature on neoplasia in reptiles, and focuses on advanced diagnostics and therapeutic options for reptilian patientssuffering neoplastic disease. Although most applied clinical reptile oncology is translated from dog and cat oncology, considerations specific to reptilian patients commonly encountered in clinical practice (turtles, tortoises, snakes, and lizards) are presented.
... Neoplasms are frequently encountered in the practice of reptile medicine, although they were once considered uncommon [1]. Most data about the occurrence of neoplasms in captive reptiles originate from specialty diagnostic services [1][2][3][4][5], and considerable variation in prevalence data, ranging from 9.8% to 26%, is reported [1][2][3][4][5][6][7]. In general, neoplasms are more frequently observed in snakes and lizards in comparison to chelonians and crocodilians [1,2,[4][5][6], with the integumentary, hepatic, and musculoskeletal systems being the most commonly affected sites [1,2,[4][5][6]. ...
... In addition, IHC aids in tumor staging, selecting optimal treatment protocols, and identifying genetic variants in humans, dogs and cats [25][26][27][28][29][30][31]. Although two mammalian alpha-keratin markers were successfully used to characterize SCCs in loggerhead sea turtles (Caretta caretta), the limited availability of reptilian monoclonal antibodies and the lack of commercially available antibodies that cross-react with reptilian tissue continue to hamper the use of IHC in reptiles [7,[32][33][34]. ...
Simple Summary
The present study investigated the histological characteristics of 35 tumors from 21 lizards, 1 snake, 10 tortoises and 3 turtles that were initially diagnosed as squamous or basal cell carcinoma. Based on in-depth re-evaluation of the tissue characteristics, eight tumors initially diagnosed as squamous cell carcinoma were re-classified as basal cell carcinomas and three squamous cell carcinomas proved to be non-neoplastic lesions. All squamous and basal cell carcinomas were classified into distinct histological variants. To date, basal cell carcinomas have only been described in two reptile species. In the present study, basal cell carcinomas were diagnosed in seven additional species. While immunohistochemical staining with cyclooxygenase-2 and E-cadherin showed significant differences between the examined squamous and basal cell carcinomas, no immunoreactivity was observed for epithelial antigen clone Ber-EP4 and epithelial membrane antigen. The results of this study provide a proposal classification that allows the differentiation of squamous and basal cell carcinoma and their histological variants in squamates and chelonians.
Abstract
In the present study, the histological characteristics of squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) obtained from 22 squamate and 13 chelonian species were retrospectively evaluated. While the examined tissues were originally diagnosed as 28 SCCs and 7 BCCs based on histological evaluation by a specialty diagnostic service, eight SCCs could be re-classified as BCCs and three SCCs proved to be non-neoplastic lesions. In addition, all SCCs and BCCs were classified into distinct histological variants. The SCCs could be categorized as one SCC in situ, three moderately differentiated SCCs, seven well-differentiated SCCs, and six keratoacanthomas. BCCs were classified as five solid BCCs, four infiltrating BCCs, five keratotic BCCs, and one basosquamous cell carcinoma. In addition, the present study reports the occurrence of BCCs in seven reptile species for the first time. In contrast to what has been documented in humans, IHC staining with the commercially available epithelial membrane antigen and epithelial antigen clone Ber-EP4 does not allow differentiation of SCCs from BCCs in reptiles, while cyclooxygenase-2 and E-cadherin staining seem to have discriminating potential. Although the gross pathological features of the examined SCCs and BCCs were highly similar, each tumor could be unequivocally assigned to a distinct histological variant according to the observed histological characteristics. Based on the results of this study, a histopathological classification for SCCs and BCCs is proposed, allowing accurate identification and differentiation of SCCs and BCCs and their histological variants in the examined reptile species. Presumably, BCCs are severely underdiagnosed in squamates and chelonians.
... There is a single report of a melanoma in chelonians, describing a malignant melanoma of the carapace in a Hermann's tortoise (Testudo hermanni) [9]. In reptiles, melanomas usually occur in the thorax, are invasive and difficult to remove completely, and have a poor prognosis for the patient [2,10]. The diagnosis relies on patient history, physical examination, imaging exams, clinical pathology, and histopathology. ...
... Immunohistochemical analysis has been successfully used to assist differentiation of tumor types in reptiles [4]. Specifically, immunohistochemistry for melan-A and S100 was used in the diagnosis of melanomas and iridiophoromas [9,10]. In one of these studies, 10 chromatophoromas derived from snakes were labeled with S-100, PNL-2, melan-A, and HMB45, and only the malignant mixed chromatophoroma was positive for melan-A [9]. ...
Background: There are few clinical reports of melanomas in reptiles.
Case presentation: A 10-year-old male Red-footed tortoise (Chelonoidis carbonaria) was referred to the Veterinary Hospital presenting with an ulcerated mass in the lateral aspect of the left pelvic limb. Radiographs demonstrated swelling and increased soft tissue density overlying the femur, tibia, and fibula, without bone involvement. Fine-needle aspiration cytology revealed innumerable round cells, with a defined cytoplasm filled with fine brown-black granules (melanin), which were considered well-differentiated melanocytes, suggesting a case of cutaneous melanoma. The mass was surgically removed. It was encapsulated and had an abundant blood supply. Histopathological examination revealed a well demarcated and encapsulated neoplastic proliferation of mesenchymal cells, with high cellularity and moderate fibrous stroma. Lymphangiectasia in the dermis adjacent to the tumor was also observed. Immunohistochemistry confirmed the diagnosis, with cells staining positive for Melan-A antibody being observed in neoplastic proliferation, adjacent dermis, inside lymphatic vessels, and invading the delimiting tumor's capsule. There was no evidence of local or systemic recurrence of the neoplasm over 500 days after removal.
Conclusions and clinical relevance: Chelonians can be affected by cutaneous melanomas. Surgical removal in this case was curative.
... Metastatic lesions have not been found in any internal organs (Okihiro, 1988). Slight infiltration of the neoplastic cells From the available reports, curative surgical excision has been most commonly used for treatment of chromatophoromas in reptiles (Irizarry-Rovira et al., 2006;Heckers et al., 2012), however, recurrence and metastasis to the skin and viscera has been reported (Heckers et al., 2012;Lewis et al., 2015). In fish, cryosurgery was effective in treating chromatophoroma in largemouth bass (Yaw et al., 2016). ...
... Metastatic lesions have not been found in any internal organs (Okihiro, 1988). Slight infiltration of the neoplastic cells From the available reports, curative surgical excision has been most commonly used for treatment of chromatophoromas in reptiles (Irizarry-Rovira et al., 2006;Heckers et al., 2012), however, recurrence and metastasis to the skin and viscera has been reported (Heckers et al., 2012;Lewis et al., 2015). In fish, cryosurgery was effective in treating chromatophoroma in largemouth bass (Yaw et al., 2016). ...
A male Siamese fighting fish (Betta Splendens Regan) was referred with a raised mass at the basis of the dorsal fin. Most of dorsal fin rays were missing. Surgical biopsy of the mass was performed in less than 2 min and macroscopically the mass appeared to invade the underlying musculature. The fish died after 29 days. Transverse sections showed that the primary mass had expansive growth and invaded the underlying muscles. Internal examination revealed the abdominal cavity to be filled with a secondary large mass. Also white spots were observed on the liver. Squash preparations of small section of the masses showed olive to green coloured pigments that were birefringent under polarized light. Histologically, the mass consisted of neoplastic iridophores arranged in bundles with moderate amounts of cytoplasm containing olive to green pigments that were birefringent with polarized light. In most areas, the neoplastic cells invaded the underlying muscles and bone trabeculae. Microscopic metastasis, with similar morphologic features to the primary tumour, were observed in the kidney, liver, spleen, and intestine. Nuclei of metastatic cells in the kidney and liver were round to ovoid with one to three nucleoli. These metastatic cells had birefringent intracyto-plasmic olive to green pigments. A diagnosis of malignant iridophoroma was made.
... 2 Although rare, chromatophoromas in reptiles, including snakes, lizards, and tortoises, have also been studied. 7 The presence of pleomorphism, high mitotic activity, vascular invasion, and metastasis have been linked to malignant tumor behavior in reptiles. 7 By use of these criteria, the tumor in the koi of the present report was classified as malignant, yet the fish remained healthy (although emaciated) and was still alive 3 years after the time of diagnosis. ...
... 7 The presence of pleomorphism, high mitotic activity, vascular invasion, and metastasis have been linked to malignant tumor behavior in reptiles. 7 By use of these criteria, the tumor in the koi of the present report was classified as malignant, yet the fish remained healthy (although emaciated) and was still alive 3 years after the time of diagnosis. ...
... Iridophoroma or guanophoroma are uncommon, benign pigment cell tumours, characterized by spindle cells packed with coarse granulated, light refractile golden-brown to olive-green crystalline pigment platelets (Heckers, Aupperle, Schmidt, & Pees, 2012;Okihiro, 1988). ...
... Iridophoromas are whitish or metallic silver in colour (Okihiro, 1988;Singaravel et al., 2016). Similarly, this present investigation with a whitish lesion was reported for the first time in R. kanagurta; this type of iridophoroma has an invasive growth, but no gross evidence of distant metastasis (Heckers et al., 2012;Okihiro, 1988). Gross pathological examinations of the distended noninvasive and exophytic neoplastic growth led to the suggestion of the benign character of this neoplasm. ...
... When examined under polarised light microscopy, melanophores do not exhibit birefringence, which occurs only in chromatophores that contain crystallinereflecting organelles, such as iridophores, but is not observed in melanophores (Jacobson et al., 1989;Irizarry-Rovira et al., 2006). This feature enabled us to accurately diagnose the type of chromatophoric neoplasm observed (Irizarry-Rovira et al., 2006;Heckers et al., 2012). ...
Melanophoromas, rare neoplasms of melanophores, have been recorded in a limited number of amphibian species. This study documents the first reported case of melanophoroma in the Criolla Frog (Leptodactylus latrans), presenting a detailed analysis of its macroscopic and microscopic features. The specimen, collected in São João da Barra, Rio de Janeiro, Brazil, exhibited a solitary blackened lesion on the dorsolateral region. Histological examination revealed a non-encapsulated neoplasm with high cellularity, expansive and infiltrative behavior, and melanophore differentiation. The absence of mitotic activity and limited pleomorphism characterized the tumor as a spindle-cell melanophoroma. Despite prior preservation of the specimen in formalin, which precluded a definitive determination of etiology, potential causes such as environmental, viral, or genetic factors are discussed. This study highlights the role of herpetological collections in advancing our understanding of pathologies in wild amphibians and underscores the need for further research into the underlying mechanisms of amphibian neoplasms.
... 1 Most data about the occurrence of neoplasms in captive reptiles originate from specialty diagnostic services, 1-5 and a considerable variation in prevalence data, ranging from 9.8% to 26%, has been reported. [1][2][3][4][5][6][7] The increasing number of neoplastic disorders diagnosed in captive reptiles might at least be partly attributed to the facts that reptile pet owners more readily seek veterinary advice that there is increasing availability and use of advanced diagnostic tools. 5 Moreover, the increasing lifespan of reptile pets as well as predisposing environmental and genetic risk factors may also contribute to this seemingly increasing prevalence. ...
Background
Squamous cell carcinoma (SCC) is one of the most commonly diagnosed neoplastic disorders in reptiles. Recently, however, it has been demonstrated that basal cell carcinomas (BCCs) are frequently misclassified as SCCs. Several histological SCC and BCC variants have been characterised and their classification may allow the establishment of appropriate prognosis estimation and treatment approaches.
Hypothesis/Objectives
To describe the clinical features and surgical outcomes of SCCs and BCCs diagnosed between 2010 and 2022 in reptiles.
Animals
Thirty‐three captive reptiles (21 squamates and 12 chelonians).
Materials and Methods
Detailed clinical history, including staging and surgical outcomes, were performed. Statistical analysis assessed significant factors using prism (v8.2.1).
Results
While SCC was predominantly diagnosed in lizards, BCC was most commonly diagnosed in chelonians, and both neoplasms mainly occurred in adult to aged, male individuals. Although the gross pathological findings were highly comparable between SCC and BCC, considerable variation could be seen according to the primary location (oral, cutaneous or epidermis of the shell). Humane euthanasia or noncurative intent surgeries were performed in a minority of the cases. Curative intent surgeries were successful in 19 of 27 cases during a 1‐ to 7‐year follow‐up period, yet recurrence was seen in 8 cases. The results of this study allowed the identification of significant high‐risk prognostic factors for SCC and BCC in reptiles.
Conclusions and Clinical Relevance
This study contributes to predicting the clinical behaviour and prognosis of distinct SCC and BCC histological variants, and selecting the most appropriate treatment protocol.
... While S100 immunolabeling has been observed in mammalian neuroendocrine tumors, its broad cellular expression hampers its diagnostic specificity (19). In reptiles, S100 has been previously used to successfully label chromatophoromas and various mesenchymal tumors (fibroma, myxoma, myxosarcoma) in different species (20), and a peripheral nerve sheath tumor in a bearded dragon (21), which are not morphologically compatible with this case. The diagnostic significance of S100 immunolabeling in this case, together with the negative tumoral staining on the second round of immunohistochemical characterization, is therefore questionable and does not help to identify the potential cellular origin of this neoplasm. ...
This article describes the diagnostic, treatment and attempted characterization of a neoplasia of undetermined origin in a Asia minor spur-thighed tortoise. A 21-year-old male Asia minor spur-thighed tortoise (Testudo graeca ibera) was admitted for a 4-month history of diarrhea, and a 2-month history of anorexia and lethargy. Physical examination revealed a firm midcoelomic mass in the right prefemoral fossa. Blood biochemistry indicated hypocalcemia and mild elevation of aspartate aminotransferase. Supportive care was administered in the form of heating, baths, and calcium injections. Ultrasound examination of the coelomic cavity revealed a 6-cm diameter, highly vascularized mass with liver-like echogenicity. Neoplasia was suspected, and endoscopy was performed, revealing a brown circumscribed mass with smooth edges. Surgical removal of the mass was evaluated by CT scan and achieved via a plastrotomy; however, the patient died 1 day post-surgery. The mass was located on the dorsal right side of the coelomic cavity in the anatomic location of the right testicle. Histopathology revealed neoplastic cells organized in packets supported by fibrous septa. Neoplastic cells showed moderate and inconsistent positive immunohistochemical labeling for S100 and NSE, and negative immunohistochemical labeling for pan-cytokeratin, vimentin, CD3, CD79a, chromogranin A, and synaptophysin. The prominent histological and anatomical characteristics of the mass indicated a possible testicular or neuroendocrine (e.g., adrenal gland) origin. Due to inconclusive immunohistochemical profiles and poorly differentiated neoplastic cells, only a final diagnosis of intracoelomic malignant tumor of undetermined origin could be established. This case underscores the difficulties encountered in achieving definitive diagnoses of neoplastic diseases in reptile medicine.
... Therefore, the gene carrying the Lemon Frost mutation is expected to play a role in iridophore proliferation. It is worth noting that iridophoromas are known to naturally occur in multiple species of reptiles (67,68). ...
While there are more than 10,000 reptile species, and reptiles have historically contributed to our understanding of biology, genetics research into class Reptilia has lagged compared to other animals. Here, we summarize recent progress in genetics of coloration in reptiles, with a focus on the leopard gecko, Eublepharis macularius. We highlight genetic approaches that have been used to examine variation in color and pattern formation in this species as well as to provide insights into mechanisms underlying skin cancer. We propose that their long breeding history in captivity makes leopard geckos one of the most promising emerging reptilian models for genetic studies. More broadly, technological advances in genetics, genomics, and gene editing may herald a golden era for studies of reptile biology.
... Clinical signs vary depending on tumour type and its lo-cation, therefore a broad complex of diseases including neoplasia have to be considered in patients suffering from anorexia and lethargy. In reptiles diagnosed with neoplasia, the most common symptoms include lethargy, anorexia, dyspnoea, presence of cutaneous masses, coelomic distension, constipation, or paresis/paralysis (Hernandez- Divers and Garner 2003;Cruz Cardona et al. 2011;Hannon et al. 2011;Heckers et al. 2012). Based on a necropsy review, captive reptiles have an incidence of neoplasia comparable with that of mammals and birds (Effron et al. 1997). ...
The 16-year-old female leopard gecko (Eublepharis macularius) was presented with distended coelom and cachexia. Examination of the faecal sample ruled out the presence of protozoan parasites. A radiographic examination confirmed the presence of radiopaque foreign material in the intestine. The conservative treatment with tramadol, butylscopolamine, famotidine, vitamin B complex, and supportive fluid therapy with Hartmann solution and Duphalyte, was performed for 14 days. Ultrasonographic examination revealed the presence of a large mass adherent to the liver (with hypoechoic regions), a thin-walled cystic structure close to the liver, and coelomic effusion. Surgical exploration revealed a large mass on the right ovary. The unilateral (right) ovariectomy was performed. Histologic examination of the mass revealed dysgerminoma with an invasion of the ovarian bursa and blood vessels. Nine months after the surgery the patient was active and doing well. In reptiles, dysgerminoma is an uncommon type of neoplasia. To the best of our knowledge, this is the first case of dysgerminoma tumour diagnosed intravitally and treated successfully in lizards.
... This is supported by the fact that some of the scales at either end and along the edges of the injury are formed correctly but without the correct colour, whereas some scales are deformed and coloured correctly. More specifically, the observation fits the definition of a benign iridophoroma (Heckers et al., 2012). Chromatophoromas, including iridophoromas, can appear simply as abnormally pigmented scales, including unpigmented and bright white, or they can form extensive lesions (Colleen Monahan, in litt.). ...
In the present we report an unusual white lesion on the dorsum of a D.
russelii individual from the Surat district, Gujarat State, India
... 90 Out of 69 reptiles, heliophilic species seemed to be more prone than nocturnal species to develop pigment-cell tumors. 91 Due to the design of the study, however, which did not include a control group, the assumption made by the authors that UV exposure and development of these tumors could be associated 90 should be interpreted with caution. Owners who agree to a necropsy of their reptiles may be more educated and thus more prone to buy UVB lights for their reptiles, thus explaining that 60% of reptiles with pigment-cell tumors had a UVB light in their enclosure. ...
Many animals under human care are kept indoors to prevent infectious diseases vectored by wildlife, facilitate environment control, or due to the lifestyle of their owners. However, ultraviolet radiation has documented effects on animal vision, vitamin synthesis, immunity, behavior, psychogenic disorders and on their environment. Ultraviolet-emitting lights are commercially available and the documentation of their effect on indoor-housed animals is increasing. This article reviews published information about ultraviolet effects in vertebrate animals from veterinary and ethological perspectives, and techniques used to assess ultraviolet exposure across animal taxa.
... SCC diagnosis in reptiles is based mainly on the histological characteristics [18,19,21]. Immunohistochemical characterization of neoplastic cells in reptiles has been reported rarely due to the lack of cross-reactive commercial antibodies [30][31][32][33]. In fact, the only attempt to characterize SCCs in reptiles failed [26]. ...
Background:
Cytokeratins with epitopes in common with those of alpha (acidic and basic) mammalian keratins have been immunohistochemically demonstrated in the epidermis of reptiles. However, there are no reports of immunohistochemical staining patterns of alpha-keratins in other tissues from reptiles. Because the epithelial tumours usually retain the keratin patterns of their normal epithelial origin, it is necessary to know in advance these patterns in the major normal epithelia and organs. We used anti-alpha human keratin AE1 and AE3 monoclonal antibodies to study the staining patterns of alpha-keratins in the major normal epithelia and organs from two reptile species [the bearded dragon (Pogona vitticeps) and the loggerhead sea turtle (Caretta caretta)]. We also studied the immunolocalization of alpha-keratins in squamous cell carcinomas (SCCs) in a bearded dragon and two loggerhead turtles.
Results:
Acidic alpha-keratin (AE1 positive) was detected in many of the epithelial tissues of the bearded dragons; however, the detection of basic alpha-keratin (AE3 positive) was much more limited. Alpha-keratins were detected in a greater number of tissues of loggerhead turtles compared with those observed in bearded dragons. In the bearded dragon SCC, all layers of the nests of neoplastic cells, including the cornified layer of the keratin pearls, were strongly reactive with the AE1 antibody. However, a weak reactivity using the AE3 antibody was detected in the basal and intermediate layers of these nests. In the cutaneous SCCs of both sea turtles, acidic alpha-keratin was detected in the basal and suprabasal layers, and in all of the invasive neoplastic cords, while basic alpha-keratin was mainly detected in the invasive neoplastic cords. The pattern observed in the metastases in both turtles consisted of immunohistological detection of acidic alpha-keratin in all metastatic foci, and limited or lack of detection of basic alpha-keratin.
Conclusions:
This study provides, for the first time, information about the immunohistochemical staining patterns of alpha-keratins in normal tissues from bearded dragons and loggerhead sea turtles, and confirms the usefulness of AE1 and AE3 monoclonal antibodies in these reptile species. The use of these antibodies also contributed to a better characterization of SCCs in these species.
... 6 Chromatophoromas in reptiles. 7,8 These are tumors that arise from pigment cell, and most commonly occur in the skin. ...
The common diseases are listed, with clinical presentations. Appropriate diagnostic tests will be reviewed, as well as review of anatomy and necropsy lesions.
Learning Objectives: To develop a practical DDX list for the sick pet presenting to the veterinarian
... 2,6,8,9 Of the 18 different tumor types reported here, 17 have been reported previously. [2][3][4]7,10,11 To the authors' knowledge, however, this is the first report of an astrocytoma in a snake. Astrocytomas are neuro- glial cell tumors of the central nervous system that are relatively common in dogs. 1 In this study, we found that a greater percentage of the malignant neoplasms were of mesenchymal origin (i.e., ''sarcomas''). ...
A retrospective study was conducted to review neoplasia of captive snakes in the Zoo Atlanta collection from 1992 to 2012. Of 255 snakes that underwent necropsy and histopathologic examination at Zoo Atlanta during the study period, 37 were observed with neoplasia at necropsy. In those 37 snakes, 42 neoplastic lesions of 18 primary cell types were diagnosed. Thirty-five of those neoplasms (83.3%) were malignant, and of those, 19 were of mesenchymal origin, whereas 14 were of epithelial origin. The median annual rate of neoplasia at necropsy was 12.5% (interquartile range = 2.8–19.5%) over the 21-yr study period. The mean estimated age at death for snakes with neoplasia was 13.2 yr (range, 1–24 yr). Investigating the incidence and clinical significance of neoplasia in captive snakes is vital for developing effective preventative and treatment regimes.
... When compared across species, lizards exhibited the highest frequency with 20%, corresponding to 14% melanophoromas and 6% iridophoromas. Snakes had the second highest frequency (10%) with all being melanophoromas, followed by turtles/tortoises (8%), also having all melanophoromas [29]. ...
Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1) that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus . Our results provide insight into pigment phenotypes in pythons.
... Melan A is used in mammalian medicine to differentiate adrenocortical and renal carcinomas (Ghorab et al., 2003). It is also a potent marker for melanoma in mammals and has been applied to melanophoromas in reptiles (Heckers et al., 2012), but to the authors' knowledge has not previously been applied to adrenal tumors of snakes. In this snake, melan A staining was noted in tumor cells but not in adjacent renal parenchyma. ...
An 8-yr-old intact male woma python (Aspidites ramsayi) presented for a caudal coelomic mass effect of 3 wk duration. Ultrasound and fine needle aspiration with cytology failed to identify the source of the mass. Exploratory surgery found a 10-cm diameter, lobulated, cystic mass closely associated with the left kidney. Tumor resection with left adrenalectomy and left nephrectomy was performed. Histopathologic examination identified an adrenal interrenal cell (cortical) adenocarcinoma with adjacent renal fibrosis. The snake recovered from surgery uneventfully and was clinically healthy over an 18 month follow-up period. Eleven months postsurgery a contrast-enhanced coelomic computed tomography scan was performed to evaluate the snake for metastatic disease or local recurrence. No metastases were identified, but local recurrence was not definitively ruled out and continued monitoring of the surgery site was recommended. Eighteen months postsurgery an ultrasound examination of the snake revealed significant tumor regrowth. Because of the recurrence of disease, no further treatment was pursued.
Simple Summary
Neoplasia is a complex disease that affects many species across the animal kingdom, including lizards. Currently, cancer in lizard species is an understudied part of veterinary medicine. In this study, we focused on identifying factors that could aid in improving patient care and quality of life for lizards with neoplasia. We identified multiple factors including species, type of neoplasia, and type of treatment significantly associated with both positive and negative outcomes for lizards affected by different types of neoplasia. Specifically, we tested for statistical associations between eight clinical factors and patient outcomes. We used reported cases of neoplasia in lizards from published papers, as well as a clinical oncology database for exotic animal species. We also identified a subset of neoplasia types that were not associated with death due to their neoplasia. Our results highlight the importance of determining variables that aid veterinarians in deciding the most appropriate care for their patients. We expect that future research in this area will improve our understanding of neoplasia in lizards and better improve the identification of predictor variables for improving patient outcomes.
Abstract
Neoplasia has been reported in lizards, but more research is needed to accurately document the prevalence and prognosis of the various known neoplasms that affect lizards. This study reviewed medical records from an online database, the Exotic Species Cancer Research Alliance (ESCRA), and reviewed published literature to determine the prevalence of neoplasia, malignancy, metastasis, treatment strategies, and outcomes by species and sex. Records from 55 individual lizards, 20 different species, and 37 different tumors were identified. In the literature, 219 lizards, 59 species, and 86 unique tumors were identified from 72 published case reports. Potential signalment factors such as age, sex, and species were evaluated to see if they affected case outcome. Additional factors including neoplasia type, presence of metastasis, and types of pursued treatments were also evaluated. Statistical analysis was performed to determine whether a factor was significantly associated with animal death due to the identified neoplasia or with animal survival or death due to other causes (non-neoplastic outcomes). Komodo dragons and savannah monitors were more likely to die from neoplasia compared to other lizard species. Cases where the status of metastasis was unknown were significantly associated with death due to neoplasia. Having an unknown status of male versus female was significantly associated with non-neoplastic outcomes of death. Leukemia and islet cell carcinoma were significantly associated with death due to neoplastic causes. Chondrosarcoma, myxosarcoma, osteosarcoma, and squamous cell carcinoma were significantly associated with non-neoplastic outcomes of death. Surgery alone and radiation therapy alone each were significantly associated with non-neoplastic outcomes of death, while lizards not receiving treatment were significantly associated with death due to neoplasia. Benign neoplasia was significantly associated with non-neoplastic outcomes of death. These results will aid in the improved diagnosis and management of neoplasia in lizard species, as well as expanding our understanding of prognostic indicators of neoplasia in lizards.
Melanophoroma is a neoplasm of reptilian pigment cells, considered uncommon and part of a group of neoplasms called chromatophoromas. The objective of this work was to describe a case of melanophoroma in a free-living Lichtenstein's green racer snake (Philodryas olfersii), presenting with an ulcerative nodular neoformation in the integument of the head region. In the neurologic evaluation, a proprioceptive deficit was observed. Ultrasound, X-ray, and mass cytology examinations were performed. Radiographic and ultrasound findings of the tumor indicated infiltrative behavior, and cytology indicated a presumptive diagnosis of a melanocytic neoplasm. Based on the results of the examinations and the patient's clinical condition, euthanasia was chosen. At necropsy, there was a nodule measuring 4.5 × 2.5 × 2.0 cm, with a blackish-colored cut surface, mottled by gray areas, which infiltrated soft tissue and bone, and extended dorsally from the mouth to the cervical musculature. On microscopy, a non-delimited, non-encapsulated, and invasive neoplastic proliferation was observed, with moderate cellularity, which was predominantly composed of fusiform cells with distinct borders and foci of epithelioid cells. The cells had ample cytoplasm, which had a brown to black (melanocytic) granular pigment compatible with a melanophoroma. To the best of the authors' knowledge, this is a unique description of a melanophoroma in P. olfersii.
A 14-yr-old Argentine horned frog (Ceratophrys ornata) presented for evaluation of a chronic, cutaneous mass. A white, semifirm raised mass was present in the skin on the right cranial dorsum. Excisional biopsy was performed. Fine-needle aspiration cytology and histopathology were consistent with an iridophoroma, a type of chromatophoroma. Recurrence occurred and removal was repeated 4 months and again 2 yr following the initial surgery. The original mass did not have definitive criteria of malignancy but did extend to surgical margins, which may account for repeated local recurrence. Although chromatophoromas are relatively common cutaneous neoplasms in reptiles and amphibians, iridophoromas are rarely reported in amphibians. This is the first report of an iridophoroma in an Argentine horned frog.
This chapter contains practical discussions of herptile hematology case studies, providing information on their signalment, history, physical examination, and hematology and plasma biochemical results. The case studies covered include snake with nasal discharge and mites; snake with neurologic behavior and skin nodules; and lizard with limb lameness, lethargy, and anorexia. The chapter provides a comparison of two chelonian respiratory cases and presents case series of chelonian dystocia and follicular stasis. The discussions are supported by high‐quality images. The chapter is an essential reference for veterinary clinical pathologists, anatomic pathologists, clinicians, and technicians, as well as for veterinary students taking courses involving exotic hematology and cytology.
Interpretation of cytological preparations from herptiles is like that of birds; therefore, avian cytodiagnosis is a useful guideline for herptile cytodiagnosis. Normal exfoliation of the superficial cells of the epithelium lining the upper alimentary tract reveals normal, mature squamous epithelial cells. The reptilian cloaca consists of three compartments: the coprodeum, the urodeum, and the proctodeum. The respiratory tract of reptiles varies somewhat among the different species. Heterophilic inflammation of reptiles is represented by a predominance of heterophils in the cytological sample. Macrophagic inflammation consists primarily of macrophages with multinucleated giant cells and lesser numbers of other inflammatory cells. Septic inflammation is indicated by the presence of bacteria within leukocytes. Ovarian cystadenocarcinomas and adenocarcinomas have been reported in reptiles, commonly in the green iguana. Mycoplasmosis is the most important chronic infectious disease of wild and captive North American and European tortoises. Mycobacteriosis is an important cause of morbidity and mortality in amphibians, especially those in captivity.
The squamates (lizards and snakes) are close relatives of birds and mammals, with more than 10,000 described species that display extensive variation in a number of important biological traits, including coloration, venom production, and regeneration. Due to a lack of genomic tools, few genetic studies in squamates have been carried out. The leopard gecko, Eublepharis macularius, is a popular companion animal, and displays a variety of coloration patterns. We took advantage of a large breeding colony and used linkage analysis, synteny, and homozygosity mapping to investigate a spontaneous semi-dominant mutation, “Lemon Frost”, that produces white coloration and causes skin tumors (iridophoroma). We localized the mutation to a single locus which contains a strong candidate gene, SPINT1, a tumor suppressor implicated in human skin cutaneous melanoma (SKCM) and over-proliferation of epithelial cells in mice and zebrafish. Our work establishes the leopard gecko as a tractable genetic system and suggests that a tumor suppressor in melanocytes in humans can also suppress tumor development in iridophores in lizards.
Myxoma is a benign mesenchymal tumor of skin and soft connective tissues considered to be of fibroblastic origin. A female bearded dragon (Pogona vitticeps) with a raised mass on the left side of the body was referred to the Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. The mass had become evident and grew more extensive within the previous 11-month period. The dragon was anesthetized with 5.00% isoflurane, and the mass was removed surgically. Tissue samples of the mass were fixed in 10.00% neutral buffered formalin, sectioned and stained with Hematoxylin and Eosin (H&E), Alcian blue (pH: 2.50), and periodic acid Schiff (PAS) staining techniques. The patient was administered meloxicam, lincomycin, and marbofloxacin. Histopathologically, the capsulated mass was composed of myxoid structure. Stellate-to-reticular cells distributed in a mucinous stroma containing few tiny blood vessels were seen. Myxoid cells displayed a PAS-positive cytoplasm. The myxomatous matrix was alcianophilic at the pH of 2.50. To our knowledge, this is the first report of surgery, treatment, and histopathological study of myxoma in a bearded dragon (P. vitticeps). The sutures were also removed 12 days after the operation. No new growth of the mass was observed three months following the surgical procedures.
Coloration patterns promote survival and reproductive success in the animal kingdom. Despite their importance, wide gaps exist in our understanding of the genetic and evolutionary mechanisms that underpin them. The leopard gecko, Eublepharis macularius, is a popular companion animal, and displays a variety of coloration patterns. We investigated a spontaneous semi-dominant mutation, known as "Lemon Frost", that causes extensive white color in leopard gecko skin. Although "Lemon Frost" individuals are aesthetically appealing, more than 80% of them develop tumors of white color (i.e., iridophoroma) 0.5 to 5 years after birth. To identify the gene that regulates white color and is likely also responsible for the iridophoroma, we genotyped 220 animals, including 33 homozygous mutants, with short-read sequencing. We used synteny, linkage analysis and homozygosity mapping to localize the mutation to a strong candidate gene, SPINT1, a tumor suppressor previously implicated in human skin cutaneous melanoma (SKCM) as well as in over-proliferation of epithelial cells in mice and zebrafish. Our work establishes the leopard gecko as a tractable genetic system and suggests that a tumor suppressor in melanocytes in humans can also suppress tumor development in iridophores in lizards.
A Himalayan Rex guinea pig was presented with a history of nodular, partially ulcerated masses in the subcutis of the left shoulder. Histological examination revealed a garland-like to nodular, infiltrative neoplastic mass of the epidermis and hair follicle epithelium, which obscured the dermoepidermal junction. Neoplastic cells were immunopositive for S100, PNL-2, vimentin and melan-A antigens. No immunolabelling of CD3, CD79, Iba-1 or pancytokeratin was observed. This is the first detailed description of spontaneous amelanotic malignant melanoma in this species.
Geckos are a large infraorder of small lizards that comprise over 1300 species. The leopard gecko (Eublepharis macularius) is by far the most popular species of captive gecko. This chapter discusses the husbandry, clinical conditions, basic intervention techniques, common infectious and non‐infectious conditions of various species of geckos, including Tokay geckos, Day geckos, mourning geckos, African fat‐tail geckos, and crested geckos. The basic intervention techniques include nutritional support, anaesthesia, fluid therapy, and euthanasia. The non‐infectious conditions cover anorexia, nutritional secondary hyperparathyroidism, ophthalmic disease, neurological disease, and reproductive disorders. The infectious conditions include endoparasites, dermatitis, and viral infections. Preventative health measures are limited in geckos. In most cases focus is mainly on intestinal parasite screening and maintaining good standards of husbandry to reduce incidence of many of the common diseases.
Cytology is a simple and rapid diagnostic tool with benefit to birds and reptiles, since clinically overt disease in these species is often not evident until advanced stages. Reptiles (Sauropsida ) with over 20 000 extant species include the Dinosauria of which the birds are the only surviving members. For the purpose of discussion in this chapter, they will be referred to as birds and (non‐avian) reptiles. Since hemodilution is commonly present in cytologic samples, some unique species‐specific features regarding blood cells are considered. Although reptiles and birds are vastly different from mammals in many aspects of biology and physiology, similar standard principles of cytologic evaluation apply across all species with due consideration of major differences in inflammatory responses, prevalence of infectious agents, and frequency and type of tumor types by species. Cytologic findings require interpretation in context of relevant clinical findings, administration of current or recent medications, and other available diagnostic results.
Green iguanas are arboreal lizards, common as pet animals and in captivity. Knowledge of neoplasms in iguanas is scarce, and a challenge to their prevention, treatment, and prognosis. A captive green iguana showed a pigmented nasal exophytic neoplasm. Tumor cells were spindle-shaped to epithelioid with a variable amount of dark-brown or black granular melanin within the cytoplasm, and also presented cytoplasmic positivity for Melan-A and S100. Transmission electron microscopy evidenced intracytoplasmic melanosomes and premelanosomes and provided a definitive diagnosis of a nasal melanophoroma. Full characterization of the clinicopathological and ultrastructural features of the melanophoroma may contribute to the limited knowledge concerning cutaneous neoplasms in green iguanas.
A 1-year-old, female intact crested gecko was evaluated because of skin discoloration on her ventrum. Full-thickness biopsies were taken and evaluated histologically. Multifocally and regularly, there were collections of birefringent, granular material, localized primarily to the most superficial dermis subjacent to the overlying epithelium, throughout the length of examined sections. Polarized illumination revealed birefringent iridophores. This case either represents a benign aggregation of iridophores or simply regions of variable depigmentation, which may be considered as differential diagnoses when geckos are presented with similar clinical signs.
Many studies have evaluated various prognostic markers for canine melanocytic neoplasms either as primary or secondary goals; however, design, methodology, and statistical validation vary widely across these studies. The goal of this article was to evaluate and compare published canine melanocytic neoplasm studies in relation to the principals established in the Recommended Guidelines for the Conduct and Evaluation of Prognostic Studies in Veterinary Oncology. Based on this evaluation, we determined which parameters currently have the most statistically supported validity for prognostic use in canine melanocytic neoplasia. This information can also be used as part of evidence-based prospective evaluations of treatment regimens. Additionally, we highlight areas in which the current data are incomplete and that warrant further evaluation. This article represents an initiative of the American College of Veterinary Pathologists' Oncology Committee and has been reviewed and endorsed by the World Small Animal Veterinary Association.
An adult terrestrial garter snake (Thamnophis elegans terrestris) had 11 firm, nodular, nonfluctuant, subcutaneous swellings along its body. Several of the nodular masses were excised. The lesions consisted of heavily pigmented tumor cells and were interpreted to be malignant chromatophoromas (melanomas or erythrophoromas). Naturally occurring neoplasms in reptiles are discussed. The black/brown pigment bearing cells of poikilotherms are melanophores, the yellow/orange pigment bearing cells are xanthophores, and the orange/red pigment bearing cells are erythrophores. All these cells arise from the neural crest relatively early in the embryo; have similar morphologic features at the light microscopic level; and some of them may even contain the organelles for production of several of the pigments, depending on the hormonal milieu and possibly other factors. This tumor was called a chromatophoroma to indicate that a range of pigments was present in the tumor cells. Aside from this color distinction, the morphologic characteristics were identical to those of a melanoma.
Thin and thick sections of both physiologically active and physiologically passive iridophores from a range of vertebrate species have been examined by electron microscopy at 60 kV and at 1,000 kV. All iridophores studied have been found to contain 65-A filaments linking successive crystals in their parallel stacks; their orientation in the cell is shown in stereo pairs of 0.25-microm sections obtained from high voltage microscopy. In addition, several of the physiologically passive iridophores contain 100-A filaments in varying numbers. It is suggested that the thin filaments might be iridophore actin and play a role in the movement of iridophore components, and that the 100-A filaments might play a cytoskeletal role in the iridophores in which they occur.
S-100 proteins are abundant in melanocytes of the skin; thus, S-100 immunoreactivity has been used as a diagnostic criterion for melanoma in humans and other placental mammals. We tested cutaneous melanomas of two marsupials, a bird, and a snake for S-100 immunoreactivity, using a polyclonal rabbit antibovine S-100 antibody. The tumor from a Tasmanian Pademelon (Thylogale billaridierii) was composed of large epithelioid cells, most of which had S-100-positive cytoplasm. In general, there were only scattered individual spindle-shaped S-100-positive cells or groups of cells in the primary mass from a Spotted-tailed Quoll (Dasyurus maculatus); S-100 staining was primarily nuclear. Cells comprising the melanomas of the Australian Cormorant (Phalacrocorax carbo) and the Death Adder (Acanthophis antarcticus) were S-100-negative, although peripheral nerve bundles in both were S-100-positive.
Diagnostic records from 338 canine oral melanomas in 338 dogs received at the Veterinary Medical Diagnostic Laboratory (1992-1999) were reviewed. Of these tumors, 122 plus an additional 7 metastatic melanomas of unknown origin were selected for clinical follow-up, histologic review, and immunohistochemistry. Chow Chow, Golden Retriever, and Pekingese/Poodle mix breeds were overrepresented, whereas Boxer and German Shepherd breeds were underrepresented. There was no gender predisposition and the average age at presentation was 11.4 years. Forty-nine dogs were euthanized due to recurrence or metastasis. The average postsurgical survival time was 173 days. The gingiva and the labial mucosa were the most common sites. Most tumors were composed of either polygonal cells (27 cases, 20.9%), spindle cells (44 cases, 34.1%), or a mixture of the two (polygonal and spindle) (54 cases, 41.9%). Clear cell (3 cases, 2.3%) and adenoid/papillary (1 case, 0.8%) patterns were uncommon. The metastases of 6/6 oral melanomas had morphologic and immunohistochemical features similar to those of the primary tumors. Immunohistochemically, Melan A was detected in 113/122 oral (92.6%) and 5/7 (71.9%) metastatic melanomas. Only 4/163 nonmelanocytic tumors were focally and weakly positive for Melan A. Antibodies against vimentin, S100 protein, and neuron-specific enolase stained 129 (100%), 98 (76%), and 115 (89.1%) of 129 melanomas, respectively. Antibodies against other melanocytic-associated antigens (tyrosinase, glycoprotein 100) did not yield adequate staining. We conclude that Melan A is a specific and sensitive marker for canine melanomas.
Immunohistochemistry, using a monoclonal antibody to Melan A and a polyclonal antibody to S100 protein, was applied to 48 formalin-fixed, paraffin-embedded specimens of feline melanoma. Forty-two cutaneous, three oral, one mucocutaneous, and two metastatic melanomas comprised the tumors. Thirty-two tumors (67%) were positive for Melan A and 42 (87.5%) were positive for S100. All but one of the tumors that were positive for Melan A were also positive for S100. S100 was detected in 11 of 16 tumors that were negative for Melan A. Seventy-five percent (9 of 12) of amelanotic melanomas were negative for Melan A. Normal adrenal cortex, the cerebellum, and the skin had cells that were positive for Melan A. Sebaceous adenoma was the only nonmelanocytic tumor examined that reacted with antibody to Melan A. Although less sensitive than S100 protein, Melan A is more specific for melanoma and is useful in differentiating feline cutaneous melanoma from the more common pigmented basal cell tumor.
The laboratory records from 384 dogs with a diagnosis of either melanoma or melanocytoma were selected for study. Significant negative determinants of patient survival for melanocytic tumors were: 1) metastasis, 2) mitotic index (MI), 3) nuclear atypia, 4) tumor score, 5) increasing size/volume, 6) the presence of deep inflammation, and/or 7) intralesional necrosis. In addition to these attributes, age was a significant determinant for tumors of the skin. For the feet and lips, 8) age and 9) junction activity negatively impacted survival. Mathematic models were constructed based on these significant determinants to predict the postsurgical outcome of melanocytic neoplasia. Melanocytic oral neoplasms comprised 19% (73/384) of the neoplasms; 92% of these were classified as malignant in the biopsy report, but malignant behavior (i.e., metastasis or recurrence) was observed in only 59% of cases. The prognostic model for oral tumors based on nuclear atypia provided the most accurate (89%) prediction of overall behavior. Melanocytic tumors of the feet and lips were also 19% (73/384) of the total population. Seventy-four percent were reported malignant, whereas only 38% actually demonstrated malignant behavior. The prognostic models based on both MI or nuclear atypia had an overall correct behavioral classification of 81%. Melanocytic tumors in the skin comprised 59% (227/384) of study specimens. Although 39% were reported as malignant, only 12% exhibited malignant behavior. A satisfactory predictive model that employed MI could not be constructed, but one using nuclear atypia gave an overall correct classification in 93.3% of the cases.
It is often difficult to make the distinction between benign vascular tumours (haemangioma) and vascular tumour-like lesions (reactive vascular hyperplasia). Two granulation tissue-type pseudohaemangiomas, pyogenic granuloma and granuloma gravidarum, will be considered first.
A wild-caught subadult eastern yellowbelly racer (Coluber constrictor flaviventris) presented with three raised, circumscribed, freely moveable subcutaneous masses over the dorsal and right epaxial musculature. Microscopic examination and special staining of surgically excised masses were diagnostic for chromatophoroma. No metastases were apparent on whole-body plain film radiographs and computed tomography. Additional excisional biopsies of previously affected sites performed 13 wk later demonstrated normal skin and subcutis. The snake recovered uneventfully and continued to do well 18 mo later. Surgical excision of chromatophoromas remains the treatment of choice in snakes. Subcutaneous masses in snakes should be thoroughly investigated.
A 7 year old male Central Bearded Dragon Pogona vitticeps weighing 420gm was presented for assessment of a llmp that had deeeloped on his tail ooer the preeioos 2 months. The mass was located on the dorsal aspect of the tail approximately 12 cm from the tail base. It was approximately 2 cm in diameter, heaaily pigmented and appeared well defined from the ssrroonding tissse. It was firm to tooch and relatiiely immobile when manipplated. The lizard's tail distal to the mass showed a series of kinks thoogh the owner commented that these had been present for most of the lizard's life. There were also approximately six 3mm black raised areas scattered ooer the body. These had been present for many years and had not changed in any way according to the owner's recollection. The dragon was otherwise in excellent body condition and hhsbandry appeared adeqqate. A fine needle aspirate of the tail mass was taken and ssbmitted to Gribbles Veterinary Pathology. The microscopy resslts were "there was a moderate amoont of pale amorphoos basophilic backgroond, occasional erythrocytes and low to moderate nnmbers of indiiiddally arranged nncleated cells. These cells contained high nnmbers of black-brown melanin pigments which obsccred all other morphological feattres. There were high nnmbers of free melanin grannles within the backgroond of the smear. These findings are consistent with a mesenchymal pigmented neoplasm." These resslts were disccssed with the lizard's owner and it was addised that the tail shoold be ampptated.
The immunoreactivity of PNL2 and antityrosinase in formalin-fixed, paraffin-embedded canine melanocytic neoplasms (n = 101) was compared with that of Melan A. Of the 113 samples overall, 106 were positive for PNL2, 101 for Melan A, and 90 for tyrosinase. Six melanomas that were positive for PNL2 were negative for Melan A; 1 melanoma that was negative for PNL2 was positive for Melan A. Eighty tumors were positive for all 3 markers; 111 reacted with at least 1 the 3 antibodies. Decalcification with formic acid for up to 1 week did not affect immunoreactivity of any of the markers; however, decalcification with HCl for 1 day or 1 week notably decreased or completely abrogated immunoreactivity for Melan A and PNL2. There was only minor loss of immunoreactivity for tyrosinase in tissues decalcified with HCl for 1 week. Prolonged fixation (up to 2 months) did not affect PNL2 or tyrosinase immunoreactivity; however, Melan A immunoreactivity was reduced after 1 month of fixation. PNL2 was not expressed in 120 nonmelanocytic tumors (carcinomas, sarcomas, steroid-producing tumors, and leukocytic tumors). In summary, antibody PNL2 is slightly more sensitive than Melan A and more sensitive than tyrosinase in the identification of canine melanocytic neoplasms. Furthermore, PNL2 does not appear to cross-react with nonmelanocytic neoplasms. PNL2 is resistant to prolonged fixation but sensitive to strong decalcification. Results indicate that PNL2 is an excellent marker in the identification of canine melanomas and that the sensitivity is close to 100% when used in conjunction with Melan A and tyrosinase.
München, Univ., Diss, 2004 (Nicht für den Austausch).
For the immunohistochemical analysis of melanoma, various serological reagents are available. Melanocyte differentiation markers are reactive with cells and tumors of melanocytic lineage. HMB45 to gp100 has been the most commonly used melanocyte differentiation marker. Recently it was complemented by reagents such as antibodies to Melan-A/MART-1 and tyrosinase. Other reagents, whose reactivity is not strictly confined to melanocyte differentiation antigens, are also commonly used. Among them, the most prominent is S100. Other reagents are D5 to MITF or PNL-2. The properties of these reagents are presented, and their usefulness as markers in the setting of metastatic melanoma in sentinel lymph nodes is discussed.
The fundamentally diverse vertebrate pigment cells, melanophores, xanthophores, and iridophores, contain pigmentary organelles
known, respectively, as melanosomes, pterinosomes, and reflecting platelets. Their pigments are mealanins pteridines, and
purines. Mosaic pigment cells containing more than one type of organelle have been observed and mosaic organelles containing
more than one type of pigment have been discovered. It is proposed that the various pigment cells are derived from a stem
cell that contains a primordial organelle of endoplasmic reticular origin. This primordial organelle can differentiate into
any of the known pigmentary organelles.
Iridophoroma and melanophoroma were diagnosed in an adult male pine snake. Light microscopic examination of irregularly thickened white and black portions of abnormal scales demonstrated two distinctive populations of pigment-containing cells. Pigment cells within abnormal-appearing white scales had needle-shaped granules that were dark amber in color while black portions were composed of pigment cells typical of melanophores, with dark black, round granules. Both populations of cells showed junctional activity, and clusters of both neoplastic pigment cell types were found in adjoining areas of the epidermis. By electron microscopy, the pigment cell with amber-colored granules contained reflecting platelet profiles typical of iridophores while pigment cells with dark round granules contained melanosomes. At a junctional area between abnormal white and black scales, mosaic chromatophores containing reflecting platelet profiles and melanosomes were observed. At 1 1/2 years following initial diagnosis, the snake died and neoplastic iridophores were found at multiple visceral sites; there was no evidence of metastases of melanophores to any organ. The two pigment cell tumors are believed to have developed from either stem cells destined to become iridophores and melanophores or from prexisting iridophores and melanophores in the dermis.
A light and transmission electron microscopic study of the pigment cells (chromatophores) revealed the presence of three types of cells, namely: melanophores, xanthophores or erythrophores, and iridophores. The melanophores contained eumelanin containing organelles, the melanosomes and iridophores showed reflecting platelets, whereas, the xanthophores contained pterinosomes. Quantitatively melanophores appeared in large numbers and were widely distributed, ranging from the skin to many internal viscera, whereas iridophores were few and xanthophores very rare.
A case of malignant melanomatosis in a Florida Pine Snake (Elaphe obsoleta rossalleni) is reported and described.
Publisher Summary In addition to the presentation of positive information concerning non-melanophores, this chapter focuses on many of the ambiguities and misconceptions concerning these chromatophores. Many of these are concerned with the identification of chromatophores, whereas others, more serious in consequence, relate to errors in the elucidation of data on pigmentary substances. The chapter evaluates investigations that concerns yellow pigment cells (xanthophores), red pigment cells (erythrophores) , and reflecting pigment cells (iridophores). The major part of the discussion concerns amphibians and teleost fishes, but occasional references are made to other cold-blooded vertebrates. Non-melanin-containing chromatophores are dealt with from the standpoints of ontogeny, chemical composition, ultrastructure, and controlling mechanisms. Special attention is devoted to certain aspects of the metabolism of pigments contained in xanthophores, erythrophores, and iridophores. The most reliable diagnostic feature of a chromatophore is its color or general pigmentary appearance. Thus, a yellow pigmmt cell should be called a xanthophore and red pigment cell should be called an erythrophore. In this way, one need not determine whether the pigments are carotenoid, pteridine, flavin, or any mixture of these. With respect to iridophores, it no longer seems feasible to use the term “guanophore,” for here too the character of pigment is variable. With respect to xanthophores and erythrophores, it is now known that pteridines are contained in bodies called pterinosomes, but nothing is known about how this structure is formed or how it is related to other organelles.
Iridescent tissue colors are thought to be produced by iridophores through the optical phenomenon of thin-layer interference. Land and others have shown that structural features, predominantly reflecting platelet width and the cytoplasmic spacing between layers of platelets, determine the wavelength of light maximally reflected by this mechanism in iridophores. Some researchers have used interference microscopy to estimate these structural parameters, but the most direct measurement technique should be transmission electron microscopy (TEM). Transmission electron microscopy (TEM) has associated processing artifacts (particularly cytoplasmic shrinkage) that preclude direct measurement of ultrastructure, but if a number of assumptions are made, reflected wavelengths can be predicted. A thin-layer interference model and its associated assumptions were tested using TEM measurements of iridophores from several brightly colored tissues of each of three lizards (Sceloporus jarrovi, S. undulatus erythrocheilus, and S. magister). In all the instances examined when the contribution of the pigments present were accounted for, tissue color corresponded with predicted iridophore reflectances from the model. Finally, if the model and its assumptions are assumed to be correct, the amount of iridophore cytoplasmic shrinkage as a result of TEM processing can be calculated.
The role of immunocytochemistry in the routine diagnosis of malignant melanoma is reviewed, with particular emphasis on the potential technical and pathological interpretive problems that may occur. Careful evaluation of the appropriate panel of markers is discussed, along with details of cross-reactivity of markers with tumours of non-melanocytic derivation. Future developments in immunocytochemistry within the field of proliferation indices assessments are highlighted.
An adult female canebrake rattlesnake (Crotalus horridus atricaudatus) at Zoo Atlanta (Atlanta, Georgia, USA) had a subcutaneous mass on the left lateral abdomen. Microscopically, the tumor contained a pleomorphic population of cells with abundant intracytoplasmic brown to gold nonrefractile pigment (chromatophores), large stellate cells resembling neurons, and small stellate cells whose cytoplasmic processes formed a fibrillar matrix. The pigment stained black with the Fontana-Masson technique and was positive with the periodic acid-Schiff technique (prior to and after diastase treatment). Neuron-specific enolase was detected in the large stellate cells using an immunohistochemical staining technique. In addition, glial fibrillary acidic and S-100 proteins were detected in the chromatophores with immunohistochemical staining. The smaller stellate cells were strongly S-100 positive. Ultrastructurally, chromatophores contained intracytoplasmic structures composed of concentric lamellar membranes bordered by a triple-layer outer membrane. The morphology of these structures was compatible with pterinosomes. Three fluorescent pigments were isolated from the neoplasm by one-dimensional chromatography and characterized by spectrophotometry and spectrofluorometry.
Snake melanomas are very rare tumours in the class of Reptilia. This study demonstrates the ploidy status and S100 and HMB45 expression in snake melanomas in connection to their morphology and clinical history.
Snake melanomas are rare tumours and their pathogenesis is still unclear. In this study the expression of DNA mismatch repair genes and Growth Arrest DNA Damage Genes was investigated. The expression only of 3 of them GADD34, MLH1 and MSH2 was found. The role of these genes in animal tumorigenesis is discussed.
This retrospective study appears to be the largest publication to date regarding the prevalence of neoplasia in reptiles. As in previous publications, neoplasia is most common in snakes, followed by lizards, chelonians, and crocodilians. Several interesting trends were documented in this study, some of which appear to be previously unidentified, and some that support the findings of previous publications.
An adult, male, green iguana (Iguana iguana) of unknown age was presented with a history of an enlarging, dark, skin mass in the right axillary region. The mass was excised because neoplasia was suspected. Impression smears of the cut surface of the mass were prepared for cytologic examination, and the mass was fixed for histologic examination. The impression smears contained numerous, discrete, pigmented, neoplastic cells consistent with melanin-producing neoplastic chromatophores. Histologic findings were consistent with a cutaneous melanophoroma. By transmission electron microscopy, the intracytoplasmic pigment granules corresponded to numerous melanosomes and lower numbers of premelanosomes. Tissue sections of the tumor were immunoreactive for Melan A antigen and were negative for S-100 antigen. The cytologic, histologic, electron microscopic, and immunohistochemical findings of the neoplasm were consistent with those of melanophoroma, an uncommon neoplasm of reptiles. The present report augments the limited body of knowledge on cytomorphologic and immunohistochemical characteristics of pigmented neoplasms in reptiles.
A wild-caught subadult eastern yellowbelly racer (Coluber constrictor flaviventris) presented with three raised, circumscribed, freely moveable subcutaneous masses over the dorsal and right epaxial musculature. Microscopic examination and special staining of surgically excised masses were diagnostic for chromatophoroma. No metastases were apparent on whole-body plain film radiographs and computed tomography. Additional excisional biopsies of previously affected sites performed 13 wk later demonstrated normal skin and subcutis. The snake recovered uneventfully and continued to do well 18 mo later. Surgical excision of chromatophoromas remains the treatment of choice in snakes. Subcutaneous masses in snakes should be thoroughly investigated.
Melanoma has a wide spectrum of histologic features which mimic epithelial, hematologic, mesenchymal, and neural tumors. Immunohistochemistry has been the primary tool to distinguish melanomas from these other tumors; it has also been studied for use as an adjunct to distinguish benign and malignant melanocytic tumors and to elucidate prognosis. Furthermore, there has been extensive effort to find a suitable marker to differentiate spindle cell and desmoplastic melanoma from other tumors. We have reviewed the literature investigating melanocytic differentiation markers, proliferation markers, immunomodulatory markers, signaling molecules, and nerve growth factors and receptors. Despite the proliferation of immunohistochemical markers, S-100 remains the most sensitive marker for melanocytic lesions, while markers such as HMB-45, MART-1/Melan-A, tyrosinase, and MITF demonstrate relatively good specificity but not as good sensitivity as S-100. No marker has proven useful in distinguishing spindle cell and desmoplastic melanomas from other tumors. Ki67 remains the most useful adjunct in distinguishing benign from malignant melanocytic tumors. None of the markers reviewed has been shown conclusively to have prognostic value for melanocytic neoplasms.
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