645833

research-article2016
VDIXXX10.1177/1040638716645833Pagetoid reticulosis in an alpacaHasbach, Stern

Brief Communication

Journal of Veterinary Diagnostic Investigation

Pagetoid reticulosis (epitheliotropic 2016, Vol. 28(4) 469­–472

© 2016 The Author(s)
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DOI: 10.1177/1040638716645833
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alpaca (Vicugna pacos)

Andrea E. Hasbach, Adam W. Stern1

Abstract. A 9-year-old, intact female alpaca (Vicugna pacos) was presented for a second opinion with a 1-year history of
nonpruritic, multifocal scaling and crusted cutaneous lesions, mainly involving skin on the face, axillae, and ventral abdomen.
Clinical abnormalities were limited to the skin, and the alpaca was otherwise healthy. The initial veterinarian had examined
the alpaca, found no evidence of ectoparasites with laboratory testing, and had tried several trial therapies including oral
antibiotics, ivermectin, and topical use of betadine solution. At the time of presentation, the lesions had neither improved nor
worsened with any attempted therapy, and multiple skin biopsies were collected. Histopathology and immunohistochemical
staining findings were consistent with the pagetoid reticulosis type of cutaneous epitheliotropic T-cell lymphoma. Our report
describes the clinical, histopathologic, and immunophenotypic features of pagetoid reticulosis epitheliotropic cutaneous T-cell
lymphoma in an alpaca.

Key words: Alpacas; cutaneous epitheliotropic T-cell lymphoma; pagetoid reticulosis.

Lymphoma is recognized as one of the most common malig-
nant neoplasms affecting South American camelids
(SACs).11,20,22 Numerous publications have demonstrated the
reliability of immunophenotyping alpaca and llama lympho-
cytes using anti-human cluster of differentiation (CD)3 and
CD79α antibodies to confirm the presence of T and B lym-
phocytes, respectively, in both healthy2,4 and diseased
skin.1,8,11,16,18,20 The vast majority of cases of lymphoma
reported in SACs have involved malignant T- or B-lympho-
cyte neoplasms with dissemination to various organs.1,11,18,20
In contrast, cutaneous lymphoma (both nonepitheliotropic
and epitheliotropic) appears to be quite rare in SACs. A ret-
rospective study describing the prevalence and types of neo-
plasia diagnosed in SACs for the Pacific Northwest observed
that cutaneous and mucocutaneous neoplasms were the most
common types of tumors diagnosed in the llama and alpaca;
however, none of those cases were cutaneous lymphoma.22 A
2010 review of skin disease in the alpaca reported a single
case of subcutaneous lymphoma in a young alpaca.19 Addi-
tionally, a larger study describing the immunophenotypic
characterizations of 26 camelid malignant round cell tumors
identified a single case of epitheliotropic cutaneous T-cell
lymphoma (CTCL) in an aged llama.1
Epitheliotropic CTCL has been described extensively in
humans, more recently in dogs,5,13 and in horses.3 In these
species, epitheliotropic CTCL is a heterogeneous group of
neoplasms, which are often subclassified based on their vari-
ous clinical patterns and histologic features. In all cases, epi-
theliotropic lymphoma is characterized by a cutaneous T-cell
infiltrate with tropism for the epidermal, follicular, and/or
mucosal epithelium.21 The 3 primary classifications are
mycosis fungoides, Sézary syndrome, or pagetoid reticulo-
sis.6 Mycosis fungoides is well recognized as the most com-
mon form of CTCL in humans and domestic animals,5,13,15,21
whereas both Sézary syndrome and pagetoid reticulosis are
considered to be rare.6,13 In humans, CTCL is clonal; how-
ever, the cells have a heterogeneous immunophenotypic pro-
file.7,10,17 Our report describes the clinical, histopathologic,
and immunophenotypic features of pagetoid reticulosis epi-
theliotropic CTCL in an alpaca (Vicugna pacos).
A 9-year-old, intact female alpaca was presented with a
1-year history of cutaneous lesions characterized by nonpru-
ritic, multifocal thickening of the skin with associated scaling
and crusts. The lesions predominantly affected the perioral,
periocular, and periauricular tissue, as well as skin in the axil-
lae and on the ventral abdomen near the udder. Differential
diagnoses for this clinical presentation include dermatophyto-
sis, chorioptic mange, zinc-responsive dermatosis, cutaneous
neoplasia, idiopathic necrolytic neutrophilic hyperkeratotic
dermatosis, and less likely dermatophilosis, bacterial folliculi-
tis, as well as other ectoparasitic infestations. A previous vet-
erinarian had examined the alpaca, found no evidence of
Department of Small Animal Clinical Sciences, College of Veterinary
Medicine, Michigan State University, East Lansing, MI (Hasbach); and
Department of Pathobiology and the Veterinary Diagnostic Laboratory,
College of Veterinary Medicine, University of Illinois, Urbana, IL (Stern).
1
Corresponding Author: Adam W. Stern, Department of Pathobiology
and the Veterinary Diagnostic Laboratory, Faculty of Veterinary Medicine,
University of Illinois, Urbana, IL 61802. awstern@illinois.edu
470
Hasbach, Stern

Figure 1.  Epitheliotropic T-cell lymphoma in a 9-year-old female alpaca (Vicugna pacos). A. Note neoplastic round cells within the
follicular epithelium (thick arrows). Eosinophils are scattered in the superficial dermis (thin arrows). Hematoxylin and eosin staining of
haired skin at 200× magnification. Bar = 50 μm. B. Notice the positive membranous immunoreactivity of round cells seen within the
epidermis (arrows). CD3 immunohistochemical staining of haired skin at 100× magnification. Bar = 100 μm.

ectoparasites with laboratory testing, and had tried several trial
therapies including oral antibiotics (unknown types and
doses), ivermectin (unknown dose), and topical use of beta-
dine solution. All therapeutic trials failed to improve her con-
dition after 5 months, and the therapies were discontinued
without progression or improvement of the skin lesions.
Two months later, the alpaca was presented for a second
opinion evaluation to a veterinarian who collected several
skin biopsies and submitted them to the Veterinary Diagnos-
tic Laboratory at the University of Illinois (Urbana, Illinois).
The histopathology revealed abundant orthokeratotic hyper-
keratosis with several small aggregates of degenerative leu-
kocytes within the keratin, and a moderately hyperplastic
epidermis. The epidermis and follicular epithelium were
being infiltrated by numerous individual or aggregates of
neoplastic rounds cells (Fig. 1A). The neoplastic cells had
distinct cell margins, a large nuclear-to-cytoplasmic ratio,
round to ovoid to indented nucleus, vesiculate chromatin,
and a single prominent nucleolus. There was moderate to
marked anisocytosis and anisokaryosis with an average of 2
mitotic figures within 10 random 400× fields. Accompany-
ing the neoplastic round cells were intermediate numbers of
eosinophils within the superficial dermis with minimal num-
bers infiltrating the epidermis. Dermal and subcutaneous
neoplastic round cells were not observed. Immunohisto-
chemical staining demonstrated positive membranous immu-
noreactivity for CD3 in the neoplastic population (Fig. 1B)
and no immunoreactivity for CD79α. The histopathologic
and immunohistochemical findings were consistent with
pagetoid reticulosis epitheliotropic CTCL. Attempts to con-
tact the owners for follow-up after the diagnosis were unsuc-
cessful, and there is no further information on the progression
of lesions or the clinical state of the alpaca. To our knowl-
edge, blood work was not performed at any time during the
diagnostic evaluation of this patient.
Epitheliotropic cutaneous T-cell lymphoma is a disease
characterized by proliferating T-lymphocyte infiltration of
the epidermis and epithelium of adnexal structures.6 Mucosal
surfaces can be affected, and extracutaneous involvement
can occur with spread to regional lymph nodes, spleen, liver,
and bone marrow.21 Although no specific etiology for clonal
expansion has been identified, there is some speculation that
chronic environmental allergen stimulation or defects in the
cutaneous antigen-presenting cells may lead to progression
from chronic T-cell activation to clonal expansion of mem-
ory T cells.6 Several classification systems have been used to
distinguish between different types of epitheliotropic CTCL;
however, the classification system derived from human med-
icine is the most useful from the standpoint of histopatho-
logic differentiation. This scheme recognizes 3 distinct
subtypes: mycosis fungoides (“classic” form and “d’emblée”
variant), Sézary syndrome, and pagetoid reticulosis.
Classical mycosis fungoides typically progresses through
several distinct or overlapping clinical stages consisting of
patch and plaque formation, followed by subsequent pro-
gression to the tumor stage with potential for metastasis to
regional lymph nodes and visceral organs.14 Histologically,
mycosis fungoides is characterized by epitheliotropism of
neoplastic T lymphocytes, formation of Pautrier microab-
scesses, and pleomorphic lymphoid cells (larger mycoses
cells and smaller Sézary cells) that often form a lichenoid
band that can extend into the superficial dermis and sur-
rounding adnexal structures.6,12 Although histopathologi-
cally indistinguishable from mycosis fungoides, Sézary
syndrome is a generalized epitheliotropic T-cell lymphoma
characterized by peripheral lymphadenomegaly and the pres-
ence of neoplastic T cells (Sézary cells) within the cutaneous
tissue, lymph nodes, and peripheral circulation.21
Pagetoid reticulosis can either be localized (Woringer–
Kolopp form) with a relatively benign clinical course or gen-
eralized (Ketron–Goodman form) with a typically more
progressive nature.12 In dogs and cats, lesions are character-
ized by exfoliative erythroderma, scale formation, alopecia,
and erosions or ulcerations, without the presence of distinct
 Pagetoid reticulosis in an alpaca
masses.6 Histologically, pagetoid reticulosis can resemble
mycosis fungoides and Sézary syndrome due to the mono-
morphic lymphocytic infiltrate within the epidermis; how-
ever, the lesions are distinct from the other forms of
epitheliotropic CTCL in that the neoplastic cells are located
nearly exclusively within the epidermis and associated
appendages, without dermal or subcutaneous involvement.6,15
Lymphoma is one of the most common malignant neo-
plasms affecting SACs. Most cases of SAC lymphoma
described in the literature are multicentric, with formed masses
within the abdominal and/or thoracic cavities, and multifocal
to locally extensive masses in visceral organs, including
the liver, stomach, kidneys, heart, lungs, and lymph
nodes.8,9,11,16,18,20 In SACs, cutaneous lymphoma has only pre-
viously been reported in 2 animals. The first case involved a
1.5-year-old female alpaca with multifocal subcutaneous lym-
phoma widely distributed over the body. That alpaca was euth-
anized, and no postmortem examination was performed to
assess the presence of further organ involvement.19 The sec-
ond case involved a 20-year-old female llama with a single
subcutaneous eyelid mass. That eyelid mass demonstrated his-
tologic tropism for the epidermis, formation of Pautrier
abscesses, and prominent CD3 immunoreactivity, classifying
the mass as an epitheliotropic CTCL of the classic mycosis
fungoides form.1 Our report documents a third reported case
of CTCL in a 9-year-old female alpaca. The alpaca’s lesions
consisted of chronic and multifocal skin thickening, scaling,
and crusting predominantly affecting the tissue around the
eyes, mouth, ears, axillae, and ventral abdomen. The diagnosis
of epitheliotropic CTCL was based on the histopathologic and
immunohistochemical identification of CD3+ T-lymphocyte
infiltration of the epidermis. The absence of dermal or subcu-
taneous involvement seen in this case is consistent with the
pagetoid reticulosis form of epitheliotropic CTCL.
Lymphoma in SAC does not appear to demonstrate any
age or sex predilection, with multicentric forms having been
described in animals ranging from late gestation to 23 years
of age.11 It has been shown that lymphoma occurs at a
younger age in alpacas when compared with llamas.1,11,22
One case of subcutaneous lymphoma affected a young ani-
mal (1.5-year-old alpaca), whereas the other 2 cases of cuta-
neous lymphoma affected adult animals (9-year-old alpaca
and 20-year-old llama). In other species, the clinical course
of epitheliotropic CTCL can range from months to a few
years6; however, the small number of cases that have been
reported in SACs restricts any ability to draw reliable con-
clusions with regards to the clinical course of this disease in
camelids. As more cases are described, we will likely develop
a better understanding of the natural course of progression
for the various forms of epitheliotropic CTCL in SACs.
Authors’ contributions
AE Hasbach contributed to analysis and interpretation of data,
and drafted the manuscript. AW Stern contributed to conception
and design of the study, and critically revised the manuscript.
471
All authors gave final approval and agreed to be accountable for
all aspects of the work in ensuring that questions relating to the
accuracy or integrity of any part of the work are appropriately
investigated and resolved.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The author(s) declared that they received no financial support for
their research and/or authorship of this article.
References
1. Aboellail TA. Pathologic and immunophenotypic characteriza-
tion of 26 camelid malignant round cell tumors. J Vet Diagn
Invest 2013;25:168–172.
2. Clark MD, et al. Resident lymphocytes in the epidermis and
adnexal epithelia of normal dorsolateral thorax of alpacas. Can
J Vet Res 2013;77:63–65.
3. Durham AC, et al. Two hundred three cases of equine lym-
phoma classified according to the World Health Organization
(WHO) classification criteria. Vet Pathol 2013;50:86–93.
4. Edginton HD, et al. Resident lymphocytes in the dermis of
the normal dorsolateral thoracic skin of alpacas. Vet Dermatol
2014;25:42–45.
5. Fontaine J, et al. Canine cutaneous epitheliotropic T-cell lym-
phoma: a review. Vet Comp Oncol 2009;7:1–14.
6. Gross TL, et al. Lymphocytic tumors. In: Gross TL,
et al., eds. Skin Diseases of the Dog and Cat: Clinical and
Histopathological Diagnosis. 2nd ed. Oxford, UK: Blackwell
Science, 2005:866–893.
7. Haghighi B, et al. Pagetoid reticulosis (Woringer-Kolopp dis-
ease): an immunophenotypic, molecular, and clinicopathologic
study. Mod Pathol 2000;13:502–510.
8. Hemsley S, et al. Immunohistochemical characterization of
lymphosarcoma in two alpacas (Lama pacos). J Comp Pathol
2002;127:69–71.
9. Irwin JA. Lymphosarcoma in an alpaca. Can Vet J 2001;42:805–806.
10. Jawed SI, et al. Primary cutaneous T-cell lymphoma (myco-
sis fungoides and Sézary syndrome): part I. Diagnosis: clinical
and histopathologic features and new molecular and biologic
markers. J Am Acad Dermatol 2014;70:205.e1–205.e16.
11. Martin JM, et al. Malignant round cell neoplasia in llamas and
alpacas. Vet Pathol 2009;46:288–298.
12. Miller WH, et al. Neoplastic and non-neoplastic tumors. In:
Muller and Kirk’s Small Animal Dermatology. 7th ed. St.
Louis, MO: Saunders 2013:774–843.
13. Moore PF, et al. Canine epitheliotropic cutaneous T-cell lym-
phoma: an investigation of T-cell receptor immunophenotype,
lesion topography and molecular clonality. Vet Dermatol
2009;20:569–576.
14. Moore PF, et al. Canine cutaneous epitheliotropic lymphoma
(mycosis fungoides) is a proliferative disorder of CD8+ cells.
Am J Pathol 1994;144:421–429.
15. Morrison WB. Cutaneous lymphoma in the dog and cat. In:
Lymphoma in Dogs and Cats. 1st ed. Jackson, WY: Teton New
Media, 2004:93–100.
472
Hasbach, Stern
16. Pusterla N, et al. Multicentric T-cell lymphosarcoma in an
alpaca. Vet J 2006;171:181–185.
17. Raess PW, Bagg A. The role of molecular pathology in the diagno-
sis of cutaneous lymphomas. Patholog Res Int 2012;2012:913523.
18. Sartin EA, et al. Malignant neoplasia in four alpacas. J Vet
Diagn Invest 2004;16:226–229.
19. Scott DW, et al. Skin diseases in the alpaca (Vicugna pacos): a
literature review and retrospective analysis of 68 cases (Cornell
University 1997–2006). Vet Dermatol 2011;22:2–16.
20. Twomey DF, et al. Immunophenotyping of lymphosarcoma
in South American camelids on six British premises. Vet J
2008;175:133–135.
21. Vail DM, et al. Hematopoietic tumors. In: Withrow and
MacEwen’s Small Animal Clinical Oncology. 5th ed. St.
Louis, MO: Saunders, 2013:608–678.
22. Valentine BA, Martin JM. Prevalence of neoplasia in llamas
and alpacas (Oregon State University, 2001–2006). J Vet
Diagn Invest 2007;19:202–204.