Neoplastic diseases have been reported in a wide range of reptile taxa, including lizards, snakes, turtles, tortoises, and crocodilians [[4]]. Reported tumor prevalence varies across studies and may be influenced by species, age, sex, husbandry conditions, diagnostic access, and sampling bias [[2]]. Therefore, statements regarding tumor frequency should be interpreted cautiously [[1], [3], [5]], particularly when based on retrospective pathology submissions rather than population-level surveillance.

Earlier retrospective studies suggested differences in tumor occurrence among reptile groups [[6]]; however, contemporary data remain insufficient to establish definitive taxon-wide prevalence rankings. In clinical practice, tumors are commonly reported in captive reptiles, especially in long-lived species and animals receiving prolonged veterinary care [[3]]. In leopard geckos, increased attention has been given to pigment cell tumors, but reported high incidence is most clearly associated with specific morphs, such as Lemon Frost animals, rather than the species as a whole [[5]].

The etiology of reptile tumors is likely multifactorial. Proposed contributing factors include genetic predisposition, age, captive breeding practices, viral infection, ultraviolet exposure, chronic inflammation, hormonal influences, and environmental or husbandry-related stressors. However, direct causal evidence remains limited for many tumor types [[7]].

Genetic factors may contribute to tumor susceptibility in selected reptile lineages. In leopard geckos, SPINT1-associated alterations have been linked to iridophoroma development in the Lemon Frost morph [[5]]. This finding should be interpreted as a morph-specific observation rather than a general mechanism for all leopard gecko tumors.

Exogenous factors may also play a role. Viral-associated tumors have been reported in reptiles, suggesting a potential contribution of infectious agents in some cases [[6]]. Ultraviolet radiation has been discussed as a possible contributing factor in selected cutaneous neoplasms, although direct evidence in reptiles remains limited [[8]]. Because reptile species differ markedly in anatomy, physiology, ecology, and husbandry requirements, risk factors should be evaluated in a species-specific context.

Clinical signs of reptile tumors are variable and depend on tumor type, location, size, growth rate, and degree of local invasion or metastasis [[9]]. Common clinical findings include localized swelling, visible masses, changes in skin color or scale morphology, ulceration, bleeding, weight loss, reduced appetite, lethargy, impaired locomotion, respiratory difficulty, gastrointestinal signs, ocular abnormalities, and neurological signs [[10]].

Cutaneous tumors may be easier to recognize than internal neoplasms because they often present as raised, pigmented, ulcerated, or irregular lesions. However, not all raised or pigmented lesions are neoplastic [[11], [12]]. Therefore, suspicious lesions should be evaluated using an integrated diagnostic approach rather than clinical appearance alone.

Diagnosis of reptile tumors generally requires a combination of physical examination, imaging, cytology, biopsy, histopathology, and, when available, immunohistochemistry [[4]]. Blood biochemical testing may provide supportive information, particularly when systemic disease, organ dysfunction, or metabolic disturbance is suspected, but it is rarely diagnostic on its own.

Imaging methods such as radiography, ultrasonography, computed tomography, and magnetic resonance imaging may help define tumor location, size, tissue involvement, and possible metastasis [[13]]. Radiography is useful for skeletal involvement and gross internal masses, whereas ultrasonography may assist in evaluating soft tissue and coelomic lesions [[14]]. CT and MRI can provide more detailed anatomical information, especially for complex or deep-seated tumors, although access and cost may limit their routine use in reptile practice.

Histopathology remains central to the definitive diagnosis of reptile tumors [[15]]. Biopsy or surgical excision allows assessment of tumor architecture, cellular morphology, mitotic activity, local invasion, and surgical margins [[10]]. Representative histopathological features of chromatophoromas are illustrated in Figure 1.

Figure 1.Histopathological features ofchromatophoromaina leopard gecko.(A) (B) Cutaneousiridophoromashowing dermalinfiltration by neoplastic pigment cells.(C) (D) Liver tissue showing clusters of tumor cells.(E) (F) Renal tissue showing tumor cell infiltration.(G) Ocular tissue showing pigment cell proliferation.

Immunohistochemistry can provide additional diagnostic support, particularly in poorly differentiated or amelanotic tumors. Markers such as Melan-A and S100 have been successfully applied in reptile diagnostic pathology; however, species-specific validation remains limited and immunoreactivity may vary among studies [[16]]. Cytological evaluation may also aid preliminary assessment in selected cases, with representative features shown in Figure 2.

Diagnostic and prognostic criteria derived from human melanoma, including dermoscopic patterns, lymph-node staging, and cure-rate estimates, should not be directly applied to reptiles unless supported by reptile-specific evidence.

Figure 2.Cytological features ofchromatophoroma.Blackarrow: nucleated erythrocyte.Red arrow:iridophoromacellcontaining pigment granules.Circle: lymphocyte.

Pigmented or raised skin lesions in reptiles should be differentiated from both neoplastic and non-neoplastic conditions [[17]]. Important differential diagnoses include abscesses, granulomas, traumatic lesions, cysts, inflammatory nodules, infectious dermatitis, parasitic lesions, hematomas, epithelial tumors, mesenchymal tumors, and pigment cell tumors [[18]].

Because reptiles may form firm caseous abscesses and chronic inflammatory masses [[19]], clinical appearance alone may be misleading. Cytology, biopsy, microbial testing, and histopathology are often required to distinguish chromatophoroma from inflammatory or infectious mimics [[20]].

Surgical excision remains the primary treatment for many localized reptile tumors [[21]], especially when lesions are accessible and complete removal is feasible [[22]]. Early intervention may improve local control, reduce complications, and allow histopathological assessment of margins.

However, treatment outcome depends on tumor type, anatomical location, completeness of excision, biological behavior, and the presence or absence of metastasis. Broad cure-rate claims should be avoided unless supported by species-specific outcome data. In reptiles, published evidence is often limited to case reports or small case series, making general prognostic statements difficult [[2]].

Non-surgical treatments, including chemotherapy, radiotherapy, electrochemotherapy, cryotherapy, laser therapy, and photodynamic therapy, have been reported in selected reptile cases [[23]]. Their use should be considered case by case because evidence remains limited and responses may vary by species, tumor type, dose, and route of administration.

Chemotherapy protocols in reptiles are often adapted from mammalian veterinary oncology, but differences in metabolism, thermoregulation, renal physiology, and drug tolerance require caution [[2]]. Intralesional therapy may be considered for selected localized tumors but is unlikely to control systemic or metastatic disease [[24]]. Radiotherapy and electrochemotherapy may provide local control in specific cases [[25]], but standardized protocols for reptiles are not well established [[26]]. In other oncology settings, drug-delivery technologies and cell-death-based approaches have been explored to improve local targeting and overcome treatment resistance [[27], [28]]; however, these strategies remain conceptual references for reptile oncology rather than current clinical options.

Management should begin with tumor staging and assessment of resectability [[9]]. A practical clinical framework is outlined in Table 1 and should be adapted to species, tumor type, available facilities, and welfare considerations.

Table 1.Reported therapeutic approaches and outcomes in reptile tumors.

The integument is a common site for clinically visible lesions in reptiles [[21]]. Integumentary tumors may include epithelial tumors, mesenchymal tumors, round-cell tumors, and pigment cell tumors [[32]]. Because external lesions are often detected by owners or clinicians, they provide an important opportunity for early diagnosis.

Pigment cell tumors are especially relevant in reptiles because reptilian skin contains diverse pigment-producing cells [[33]]. Unlike mammals, reptiles may possess melanophores, iridophores, xanthophores, and other chromatophores [[34]], which contribute to their complex coloration. Neoplastic transformation of these pigment cells gives rise to chromatophoromas [[35], [36]].

Chromatophoromas are tumors derived from pigment cells. They are classified according to the predominant pigment cell lineage involved [[11], [12]]. Melanophoromas arise from melanophores, iridophoromas from iridophores, and xanthophoromas from xanthophores. Mixed chromatophoromas may contain more than one pigment cell type.

Melanophoromas commonly contain dark brown to black pigment. Iridophoromas may appear pale, white, yellow, or reflective and may contain birefringent pigment granules. Xanthophoromas are associated with yellow to orange pigmentation [[37]]. However, gross appearance alone is not sufficient for diagnosis; and histopathological confirmation is required [[10]].

Chromatophoromas typically present as cutaneous or subcutaneous masses with variable pigmentation, including dark, pale, or yellow-orange coloration depending on the predominant pigment cell type [[12]]. Lesions may appear as nodules, plaques, or infiltrative masses and may occasionally ulcerate [[6]]. Clinical presentation varies among species and tumor subtypes.

Histopathologically, chromatophoromas are composed of neoplastic pigment cells showing variable morphology, including spindle-shaped, epithelioid, or pleomorphic cells. Pigmentation may range from abundant to minimal or absent, particularly in amelanotic variants [[16]]. Mitotic activity, cellular atypia, and local invasion may vary and are not yet standardized prognostic indicators in reptiles. In some cases, metastasis to internal organs has been reported, although available data remain limited [[38]].

The biological behavior of chromatophoromas appears variable among reptile species and tumor subtypes. Some lesions may remain localized, whereas others have been reported to show local invasion or metastasis to internal organs [[21]]. Nevertheless, standardized prognostic criteria for reptile chromatophoromas have not been established, and parameters such as mitotic count, cellular atypia, local invasion, and metastasis should be interpreted cautiously due to the limited number of reported cases [[39]].

Immunohistochemistry may support the diagnosis of chromatophoromas, particularly in poorly differentiated or amelanotic tumors. Markers such as Melan-A and S100 have been applied in reptile pigment cell tumors [[35], [36]], but antibody cross-reactivity, staining consistency, and species-specific validation remain important limitations [[40]]. Therefore, immunohistochemical findings should be interpreted together with gross appearance, cytology, histopathology, pigment characteristics, and tissue distribution rather than used as standalone diagnostic criteria [[41]]. The main characteristics of chromatophoroma subtypes are summarized in Table 2.

Table 2.Key features ofchromatophoromasubtypes in reptiles.