First report of indolent cutaneous T‐cell lymphoma in a fennec fox (Vulpes zerda)

Abstract

A 10‐year‐old fennec fox (Vulpes zerda) was presented for multifocal regions of chronic alopecia and crusting. Cutaneous lymphocytosis was diagnosed through histopathological examination and immunohistochemical investigation. Clonal rearrangement of the T‐cell receptor gamma locus supports that lymphocytosis in this case was an indolent lymphoma.

A 10‐year‐old fennec fox (Vulpes zerda) was presented for multifocal regions of chronic alopecia and crusting. Cutaneous lymphocytosis was diagnosed through histopathological examination and immunohistochemical investigation. Clonal rearrangement of the T‐cell receptor gamma locus supports that lymphocytosis in this case is an indolent lymphoma.

INTRODUCTION

Cutaneous lymphocytosis is a term used to describe the proliferation of lymphocytes in the skin. Originally documented in humans, it is a rare condition in veterinary medicine, with only a small collection of documented reports in cats, and fewer in dogs. The most commonly reported cutaneous presentations in cats include focal‐to‐multifocal alopecic and erythematous regions with scale, most frequently along the lateral thorax or head and neck. ¹ , ² Cutaneous lesions in dogs are most frequently alopecia, erythema, and scale on the trunk and axilla. ² , ³ Pruritus varies, with cats more frequently reported to be pruritic than dogs. ¹ , ³

Diagnosis is based upon histopathological examination demonstrating diffuse dermal infiltration of small‐to‐intermediate lymphocytes with or without mild epitheliotropism. In cats, lymphocytes typically span from the superficial to deep dermis, while in dogs, lymphocytes are usually confined to the superficial to mid‐dermis. Approximately half of dogs and cats show mild epitheliotropism, with few areas of intraepithelial clusters of isolated to small numbers of lymphocytes. ¹ , ² This does not constitute classification of cutaneous epitheliotropic T‐cell lymphoma, which has either diffuse epithelial infiltration by neoplastic lymphocytes or multiple prominent, discrete plaques or nests of neoplastic lymphocytes infiltrating the epidermis and oftentimes adnexal structures. ⁴ The lymphocytic infiltrate in both dogs and cats is usually accompanied by smaller numbers of inflammatory cells (histiocytes, mast cells and eosinophils). Across both species, the majority of the lymphocytes are CD3‐immunopositive, with up to half of cases also having some degree of CD20‐immunopositive lymphocytes, typically forming small nodules. ¹ , ² , ³ Results of molecular clonality testing have been contradictory for both dogs and cats, with clonal rearrangement in the T‐cell receptor gamma (TRG) rearrangement locus reported as 10%–87.5% for dogs ² , ³ and 0%–70% for cats. ² , ⁵

Despite this conflicting information, most cases of cutaneous lymphocytosis in dogs and cats have a slow clinical progression with variable response to treatment. ¹ , ² , ³ Owing to the monomorphic proliferation of T cells with benign progression, it may best be classified as an indolent T‐cell lymphoma in both species. ¹ , ³ , ⁵ To the best of the authors' knowledge, this is the first published report of the condition in a fennec fox (Vulpes zerda).

CASE REPORT

A 10‐year‐old, female, spayed, fennec fox from a zoological collection was presented in November 2022 for dermatitis, alopecia and excessive licking of the hindlimb digits. After switching substrates in her habitat, the erythema around the toes resolved within 1 month; however, dry skin with adherent brown scale was then noted in the axillae. She developed multifocal patches of partial alopecia with mild generalised pigmentation, loose fine white scale and adherent brown scaling of the axillae, dorsal neck and lateral thigh over the next several months (Figure 1a,b). The skin was dry and scaly yet not erythematous, pruritic or excoriated.

FIGURE 1.

Clinical findings from a fennec fox, February 2023. (a) Right lateral recumbency: partial alopecia with mild hyperpigmentation, loose fine white and brown scale of the left axilla. (b) Dorsal recumbency: adherent brown scale, partial alopecia and hyperpigmentation extend to the sternum.

Skin biopsies were obtained from the dorsal neck and sternal region. Histopathological evaluation revealed diffuse infiltration of the superficial dermis by numerous small, mature lymphocytes, with moderate numbers of eosinophils and fewer mast cells (Figure 2a,b). Scattered lymphocytes multifocally infiltrated the epidermis. Focally in one section, the lymphocytes formed a small nodule that elevated the epidermis and extended into the mid‐dermis. The majority of infiltrating lymphocytes expressed cytoplasmic and membranous CD3 (Figure 3a). CD20 was expressed by a minority of cells within the dermal lymphocytic infiltrate, which were interpreted as reactive B cells (Figure 3b). PCR for antigen receptor rearrangements (PARR) was performed by the Leukocyte Antigen Biology Laboratory (UC Davis, CA, USA), yielding a clonal rearrangement in the TRG locus.

FIGURE 2.

Histopathological features of lesions from the sternum. (a) The superficial to mid‐dermis is diffusely infiltrated by a uniform band of small, mature lymphocytes. Haematoxylin and eosin (H&E), ×4. (b) Moderate numbers of eosinophils are multifocally admixed with lymphocytes. Small numbers of lymphocytes multifocally infiltrate the epidermis (arrows). H&E, ×20. Inset: Higher magnification view demonstrating eosinophils. H&E, ×60.

FIGURE 3.

(a) The majority of superficial dermal lymphocytes have membranous and cytoplasmic CD3 immunoreactivity. CD3 IHC, ×10. Inset: Intraepithelial lymphocytes express CD3. CD3 IHC, ×60. (b) Scattered lymphocytes within the dermal infiltrate have membranous and cytoplasmic CD20 immunoreactivity. CD20 IHC, ×10, inset ×60.

Treatment with oral prednisone, 1 mg/kg, once daily was initiated. After 1 month, the alopecia over the dorsal neck showed improvement. Approximately 2 months into treatment, the alopecia had improved, yet the fox developed a mildly decreased appetite. Clinical and biochemical changes were suspicious for a gastrointestinal ulcer, so the fox was treated with a 1‐week course of oral amoxicillin‐clavulanate (16 mg/kg twice daily) and famotidine (0.9 mg/kg twice daily). Omeprazole at 1 mg/kg was started long term with prednisone treatment. The alopecia continued to resolve, and the skin appeared unremarkable by 7 months into treatment (Figure 4a,b). Prednisone was transitioned to prednisolone (1 mg/kg) as a consequence of weight gain, and improved ability to accurately dose and administer the liquid formulation 7 months after starting treatment. At the time of death 15 months postdiagnosis, there was no recurrence of erythema or alopecia for 8 months. The fennec fox was humanely euthanised as a consequence of chronic renal disease; necropsy and histopathological investigation identified a hepatocellular carcinoma and a mild glomerulopathy with lymphoplasmacytic interstitial nephritis. Post‐mortem skin biopsies obtained from the dorsal neck and ventrum showed mild, diffuse follicular atrophy with orthokeratotic hyperkeratosis (Figure 4c).

FIGURE 4.

Clinical findings from a fennec fox, October 2023. Resolution of alopecia, scaling and hyperpigmentation in a fennec fox with cutaneous lymphocytosis following oral prednisone treatment. (a) Left neck, axilla and ventrum. (b) Left flank. (c) Post‐mortem skin biopsies showed resolution of lymphocytes and mild, diffuse follicular atrophy with orthokeratotic hyperkeratosis. H&E, ×10.

DISCUSSION

Dermatological conditions are not uncommon in captive fennec foxes; yet to the best of the authors' knowledge, this is the first published report of cutaneous indolent T‐cell lymphoma in a fennec fox or any other nondomestic species. ⁶ There have been anecdotal reports of mycosis fungoides and epitheliotropic lymphoma in this species. ⁶ The clinical presentation of alopecia and scale along the neck and axilla aligns with reported cutaneous lymphocytosis cases in dogs and cats. ¹ , ² , ³ The monomorphic and clonal T‐cell population is consistent with some reports of cutaneous lymphocytosis in dogs and cats. ³ , ⁵ This fox case of cutaneous lymphocytosis is best classified as indolent lymphoma owing to the clonal T‐cell population coupled with stable disease progression.

Published results of molecular clonality testing for cutaneous lymphocytosis in dogs and cats vary significantly depending on the study. An early study reported seven of eight dogs with a clonal T‐cell receptor (TCR) rearrangement, while a separate study in 10 dogs identified only one case with a clonal TCR rearrangement, one case having both TCR and B‐cell receptor (BCR) clonal rearrangements and four cases having a clonal BCR rearrangement. ² , ³ In one feline study, 70% from a total of 20 cases had a clonal TCR rearrangement, while a later study found no clonal rearrangements from a total of 19 cases. ² , ⁵ The discrepancy in these results may be associated with the use of different primers. Previously used TRG primers in such studies have reported sensitivities of 82% for dogs and 84% for cats, although recent advances have produced primers with sensitivities of 95.5%–100%. ⁷ , ⁸ , ⁹ , ¹⁰ Further evaluation of the clonal basis for cutaneous lymphocytosis in dogs and cats is needed, ideally with larger sample sizes and more sensitive primers.

Cutaneous lymphocytosis in humans is thought to be the result of persistent antigenic stimulation in some cases, such as insect bites, vaccines or medications, although the pathogenesis remains incompletely understood. ¹¹ A similar hypothesis has been made for dogs and cats; yet in most published cases, no cause for such antigenic stimulation before the onset of cutaneous lymphocytosis has been documented. In this fox, the resolution of the clinical signs on the digits upon changing habitat substrate, before biopsy collection, is supportive of a component of allergic dermatitis. Histologically, numerous eosinophils within the lymphocytic infiltrate may also indicate an allergic component, although infiltration by small numbers of eosinophils has been reported frequently in cases of lymphocytosis in both dogs and cats. ¹ , ² , ³ The authors speculate that the cutaneous lymphocytosis in this fennec fox may be associated with persistent antigenic stimulation associated with underlying allergic dermatitis. Atopic dermatitis is common in zoologically housed fennec foxes, typically affecting the axillae, pinnae, digits, caudal dorsum and tail base. ⁶

In humans, there is typically either spontaneous regression or slow progression of disease without metastasis; however, occasional progression to high‐grade lymphoma can occur. ¹¹ Likewise, the incidence of progression to systemic disease in dogs and cats with cutaneous lymphocytosis is low, with rare cases progressing to high‐grade systemic disease. ¹ , ² , ³ There is no consistently effective treatment for cutaneous lymphocytosis in domestic species. While some reported cases in dogs and cats demonstrated a partial or full response to treatment with oral glucocorticoids, the majority of cases demonstrated a long‐term course (typically years) with waxing and waning of clinical signs regardless of treatment. ² , ³ The resolution of clinical signs in this case following initiation of prednisone therapy along with the absence of lymphocytes in the post‐mortem skin is indicative of remission, which supports a benign process. The prognostic significance of this solitary case of remission in a novel species is, however, uncertain in the broader understanding of cutaneous lymphocytosis and indolent cutaneous lymphoma.

In conclusion, this represents the first published case of indolent cutaneous lymphoma in a fennec fox and displays characteristics that represent the features of the condition appreciated in both dogs and cats. Detection of a clonal TRG rearrangement along with remission following glucocorticoid therapy supports an indolent lymphoma, as is considered to be the case in domestic species.

AUTHOR CONTRIBUTIONS

Kristen L. Shekelle: Conceptualization; writing – original draft; writing – review and editing; resources; investigation; visualization. Alan R. Glassman: Writing – original draft; writing – review and editing; resources. Kay A. Backues: Writing – review and editing. Jennifer J. Kilburn: Writing – review and editing. Desirae A. Foust‐Wheatcraft: Writing – original draft; writing – review and editing; resources. Lauren Wood Stranahan: Conceptualization; investigation; writing – original draft; writing – review and editing; resources; project administration; supervision.

FUNDING INFORMATION

Self‐funded.

CONFLICT OF INTEREST STATEMENT

The authors have no conflicts of interest to disclose.

Shekelle KL, Glassman AR, Backues KA, Kilburn JJ, Foust‐Wheatcraft DA, Stranahan LW. First report of indolent cutaneous T‐cell lymphoma in a fennec fox (Vulpes zerda). Vet Dermatol. 2025;36:707–711. 10.1111/vde.13351

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.