NEOPLASIA 0749-0739/98 $8.00 + .

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EQUINE SARCOIDS
Laurie Goodrich, DVM, MS, Heinz Gerber, DVM,
Elaine Marti, DVM, and D. F. Antczak, VMD, PhD

Sarcoids are nonmetastatic skin tumors that constitute the most common
neoplasm of horses, donkeys, and mules. 2Y , 50, 67 These tumors adversely affect
the material value of horses, and they often compromise the use of the animal
because of their location (i.e., girth or bridle area), although they are not life
threatening in most cases. No treatment has yet been found that is universally
effective in eliminating sarcoid tumors, and recurrence of the tumor or growth
of a new sarcoid occurs frequently after therapy. This article presents summaries
of the clinical presentation and pathology of sarcoids, findings of epidemiologi-
cal and genetic studies, the evidence for a viral etiology~ and the various modal-
ities of treatment.

OVERVIEW OF CLINICAL PRESENTATION AND PATHOLOGY

Sarcoid tumors were first described and characterized as a distinct clinical

entity by Jackson. 29 Sarcoids can occur on any part of the body either singly or
in clusters. The head, ventral abdomen, and limbs are most commonly
affected. 2h ,29 The gross appearance of sarcoids can vary, and they can be classified
into four broad categories: verrucous, fibroblastic, mixed verrucous and fibro-
blastic, and flat. 5H
Sarcoid tumors characteristically show linear or focal dermal thickening
that is pale in color and firm in texture due to the fibroblastic proliferation and
the relatively few capillaries contained within the lesion. H2 The epidermis varies
from either thick, rough, and hyperkeratotic in texture to ulcerated. In a small

This study was supported by the Dorothy Russell Havemeyer Foundation, Harry M.
Zweig Memorial Fund for Equine Research, and Swiss National Research Foundation.

From the College of Veterinary Medicine, Cornell University (LG, DFA), Ithaca, New
York; and the School of Veterinary Medicine, University of Berne (HG, EM), Berne,
Switzerland

VETERINARY CLINICS OF NORTH AMERICA: EQUINE PRACTICE

VOLUME 14 • NUMBER 3 • DECEMBER 1998 607

608 GOODRICH et al

number of cases, sarcoids may appear as movable subcutaneous masses with

overlying intact skin.
Although the gross appearance of sarcoids is relatively characteristic among
equine dermal neoplasms, histopathologic confirmation is often needed to distin-
guish a sarcoid from exuberant granulation tissue (always coassociated with
sarcoids in ulcerated cases), other rare mesenchymal tUlTIOrS, habronenlatosis,
and other infectious and noninfectious granulomas." 22, 69
Observation of the entire excised tumor sectioned centrally in a plane
perpendicular to its epidermal surface is far superior to punch biopsies in
allowing the pathologist to observe the range of morphological characteristics
in a given mass and thus to arrive at the correct diagnosis. If nonexcisional
biopsy must be performed, sites within the mass must be carefully chosen to
minimize the confounding factors of surrounding inflammation and granulation
and intact epidermis.
The histologic diagnosis is based on the presence of a capillary-poor fibro-
blastic proliferation of moderate to high cell density. Individual cells are fusiform
or spindle shaped, forming whorls, interlacing bundles, and haphazard arrays
with one another. They vary from slender with elongated and pointed nuclei to
plump with large, irregular, more pleomorphic nuclei. As in most mesenchymal
tumors, cytoplasmic boundaries are ill-defined. The mitotic rate is invariably
low, but the amount of collagen varies considerably between tumors. The occur-
rence of fibroblastic orientation at a perpendicular angle to the epidermal base-
ment membrane also varies but is present in a high percentage of tumors. The
epidermis, if present, is usually hyperplastic with characteristically elongated
rete ridges, but it can be normal or even atrophic with marked hyperkeratosis,
especially in flat sarcoids.
The pathologic diagnosis of sarcoid can often be made with proper sampling
and submission of tissue for histological confirmation. An incorrect diagnosis of
fibroma, fibrosarcoma, neurofibroma, or granulation tissue may be made, thus
misleading clinicians into using overaggressive or otherwise inappropriate ther-
apy.

EPIDEMIOLOGIC STUDIES OF EQUINE SARCOID

TUMORS

Sarcoid tumors are the most prevalent neoplasms of horses. At autopsy,

about 20(% of all equine tumors have been sarcoids,h2 and at the University of
Berne and University of Zurich Veterinary Hospital, 90% of the patients affected
with skin tumors have sarcoids (Gerber H, unpublished observation, 1993).
The proportional morbidity of sarcoids in horses presented to large veteri-
nary hospitals and clinics in the United States has been estimated to be 6 per
1000.48 At the University of Berne and University of Zurich Veterinary Hospital,
sarcoid tumors accounted for 2.0% and 1.5(Yo of equine clinical cases, respectively
(Gerber H, Hermann M, unpublished observation, 1993). Sarcoid tumors ac-
counted for 0.7% of the equine clinical cases presented to the Cornell University
Veterinary Hospital between 1975 and 1987 as well as to Ohio State University
between 1976 and 1985. 45 Such clinical data are biased in that they depend not
only on the prevalence of the disease in the population but also on the value of
the affected animal, the ability of private veterinarians to successfully treat the
animals, and the expectation that the veterinary hospital is able to treat the
disease successfully. In a population survey of the Swiss Warmblood and the
 EQUINE SARCOIDS 609

Freiberger breeds, sarcoid tumors were found to occur in 0.7% and 0.4(% of
horses, respectively.17
The earliest age at which sarcoid tumors have been found is in yearlings;
however, this is rare, and tumors are usually first observed when the affected
animals are between 3 and 6 years of age. 45 Coat color has been suggested as
contributing to susceptibility, but published studies dispute this suggestion?9
Both age and gender were identified in a recent study as being significantly
associated with the development of sarcoids in donkeys.60 Young male donkeys
seemed to be at an increased risk for developing sarcoids as compared with
female donkeys. Furthermore, there was a trend towards stallions being at an
increased risk when compared with geldings; however, this was not found to be
statistically significant. The effect of castration on increasing the risk of devel-
oping sarcoids could not be discerned from the data in this study.
The reported number of tumors per horse and the distribution on the body
vary from location to location. Referral clinics in veterinary schools tend to see
cases with multiple tumors, although primary care veterinarians may often
encounter cases with only single lesions. In the northern clilnates, sarcoids seem
to be found predominantly on the head and abdomen, although in warmer
climates, the limbs are the most frequently affected parts of the body.45

ASSOCIATION OF A PAPILLOMAVIRUS AND EQUINE

SARCOID TUMORS
Studies by Olson and colleagues50 ,51 demonstrated that intradermal inocula-
tion in horses with cell-free extracts from bovine skin tumors containing bovine
papillomavirus (BPV) caused lesions that resembled equine sarcoids both grossly
and histologically. This was the earliest suggestion that sarcoids may have an
infectious origin. Subsequent studies by Ragland and coworkers 55, 56 confirmed
and extended these observations.
Field observations on an epizootic occurrence of equine sarcoid supported
these experimental studies. 57 Transmission studies using sarcoid tissue extracts,
however, were relatively unsuccessful in reproducing the disease. 8o In retrospect,
this may have indicated that the causative agent of equine sarcoids could be a
virus with a different natural host, which cannot easily be transmitted between
horses.
Experimental infection of horses with BPV induced sarcoid-like lesions
which regressed spontaneously and resulted in the production of antibodies to
the virus. Although naturally occurring sarcoids sometimes regress spontane-
ously, antibodies to BPV have never been found in horses with these tumors.
Furthermore, attempts to identify BPV virus particles in natural cases of equine
sarcoids by electron microscopy or with antibodies to the virus have been
unsuccessfu1. 5,66 This is not an unexpected finding, because the horse is not the
natural host for BPV and cannot support the vegetative portion of the viral
life cycle. 2
In one study, a retrovirus was discovered in a cell line established from an
equine sarcoid,15 but that virus was subsequently identified as an endogenous
virus unrelated to sarcoid tumors. IS Likewise, the equine cutaneous papillomavi-
rus identified by O'Banion and colleagues 49 is not thought to be related to the
equine sarcoid tumor.
Techniques of molecular biology have been applied successfully for nearly
two decades to studies of equine sarcoids, and these investigations have strongly
indicated that BPVs, or closely related viruses, are the cause of sarcoid tumors.
The first demonstration of BPV-like DNA in sarcoids came from Lancaster and
610 GOODRICH et al

colleagues. 36,37 Lancaster 35 subsequently demonstrated that the BPV-like DNA in

equine sarcoids is not integrated into the host cell.
Analysis of bovine warts from a variety of locations revealed at least six
distinct BPVs which can be divided into two groups based on histopathology.31,32
One group is associated with fibropapillomas and the other with papillomas.
The BPVs found in fibropapillomas (types 1, 2, and 5) show varying degrees of
DNA sequence homology and are the most commonly found BPV types in
equine sarcoids. 3 , 74
Angelos and colleagues 3 found a large preponderance of BPV type I-like
DNA in tumors from Swiss and US cases of sarcoid tumor. In only a few
sarcoids was BPV DNA undetectable, and no restriction patterns other than
those corresponding to BPV-l and BPY-2 were found. Importantly, BPV-like
DNA was detected in three san1ples of equine tissue diagnosed histologically as
pyogranulomatous dermatitis, fibropapilloma, and fibrosarcolna. 3 This suggested
that molecular techniques might be useful in the diagnosis of sarcoids. The
number of viral genomes per cell varied widely among the sarcoid samples
(2-800 copies per cell), but no BPV-like DNA was detected in any DNA samples
from lymphocytes from any of the sarcoid-affected horses? In Australian horses,
Trenfield and colleagues 74 found BPV-like DNA in four sarcoids that could not
be identified as BPV-l or BPV-2.
Application of blot-transfer hybridization methodology in conjunction with
restriction endonuclease cleavage patterns of viral sequences easily distinguishes
different BPYs in DNA obtained from fresh sarcoids. This technology can distin-
guish subtypes of a particular virus type or determine whether deletions, substi-
tutions, or rearrangements have occurred to the viral genome. BPV sequences in
equine sarcoids occasionally exhibit different restriction enzyme cleavage pat-
terns from those predicted from the nucleotide sequence of the prototype vi-
ruses. 3 This raises the possibility that there may be variants of BPV specific for
horses arising through mutational events. It is also possible that there may be
as yet unidentified equine papillomaviruses that are closely related to some of
the fibropapilloma BPYs.
In situ hybridization has been used to detect BPY sequences in equine
sarcoids,44 but the sensitivity of this technique is low and BPY was not detected
in many sarcoid lesions. Polymerase chain reaction (peR), a more sensitive
technique for amplification of specific DNA sequences, has been applied to
investigation of BPY in equine sarcoids. 52, 70 In these studies, over 90<X) of sarcoid
lesions were found to contain viral sequences, with the vast majority being BPV-
1 or BPY-2. In Switzerland, identical BPY sequences were found in sarcoid
lesions in horses and in naturally occurring cases of BPY infection in cattle. 52
Finally, using PCR technology, BPV sequences were found only in sarcoid lesions
and not in any unaffected areas from the same animals. 52 This strongly suggests
a causal association of BPY with equine sarcoids. Further support for this
hypothesis comes from the observation that BPY can transform equine fibro-
blasts in vitro. H5 If BPY is shown to be the etiologic agent of equine sarcoids, it
would be quite feasible to develop both prophylactic and therapeutic strategies
for prevention or treatment of equine sarcoids.
Rapid and sensitive molecular techniques such as the PCR assay could
easily be applied to the diagnosis of skin lesions that include sarcoid among the
differential diagnoses. The identification of BPY DNA in samples of affected
tissue could be made within 24 hours. The same technique could also be applied
to fixed archival samples, thus allowing retrospective identification of BPY virus
type within lesions and verification of histopathologic diagnoses.
 EQUINE SARCOIDS 611

GENETIC PREDISPOSITION TO EQUINE SARCOID TUMORS

Evidence for a genetic predisposition to sarcoids has come from several

studies. Although sarcoid tumors have been reported in virtually all equine
breeds, notable differences exist between breeds. Statistical analysis of selected
diagnoses of records from the Cornell Veterinary Hospital and Diagnostic Labo-
ratory revealed that Quarter Horses had almost twice the risk of developing
sarcoids as Thoroughbreds (odds ratio [OR] = 1.8, P < 0.05) and that Standard-
breds had a much lower risk of developing sarcoids relative to all other breeds
(OR = 0.2, P < 0.001).4 The percentage of Thoroughbreds with sarcoids was not
different from the percentage of Thoroughbreds admitted to the Cornell Veteri-
nary Hospital. Furthermore, the incidence of sarcoids in Thoroughbreds was not
different from the overall incidence of sarcoids in the hospital population.
Incidence levels below that of the Thoroughbred value of 0.70 in the Cornell
Veterinary Hospital population reflect relative resistance to sarcoids in some
breeds like Standardbreds and values above 0.70 indicate increased susceptibility.
Similarly, a low prevalence of sarcoid tumors in Standardbred horses has been
observed by others. 4h , 4H The breed distribution studies do not distinguish be-
tween environmental and genetic factors that could cause the departure from
expected values.
Other evidence for a genetic basis for sarcoid susceptibility comes from
family and population studies. The accumulation of cases of sarcoids in equine
families has been reported.3°' 57, 61 More recently, an association between sarcoid
susceptibility and the major histocompatibility complex (MHC)-encoded class-II
allele ELA W13 was reported at the population level in several breeds. 43 , 46 These
studies include estimates of the relative risk of developing sarcoids associated
with inheritance of particular MHC alleles. For the ELA W13 allele, the associ-
ated risk is in the range of those reported for many human diseases linked to
the MHC region. It must be kept in mind that most horses with the W13 allele
(and most other horses also) never develop a sarcoid tumor, however. Thus,
although the frequency of ELA W13 in sarcoid-affected horses is high, indicating
significant risk, the low overall incidence of sarcoid tumors in horses indicates
a strong environmental component to this disease. As discussed above, this
component is likely to be infection with a BPV.
Further studies in informative multiple-case families and in large half-
sibling groups demonstrated that particular ELA haplotypes segregate with
susceptibility to sarcoid tumors. II, 2], 42 The "sarcoid-susceptible" haplotypes often
(but not always) included the W13 MHC class-II antigen associated with sarcoids
at the population level. The family data are consistent with the existence of a
"sarcoid susceptibility gene" linked to the MHC region.
The ELA association demonstrated in population and family studies is one
of the strongest MHC disease associations described in any species. A similar
association between class-II MHC genes and the development of tumors induced
in rabbits by Shope papillomavirus has been described recently.25 Importantly, an
increased risk of developing papillomavirus-induced squamous cell carcinoma of
the cervix has been demonstrated in women carrying the HLA-DQw3 class-II
MHC allele. H1 It seems likely that similar virus-to-host cell interactions resulting
in oncogenic transformation may operate in these three conditions, which all
show a papillomavirus etiology and an MHC class-II association.
The precise MHC genes responsible for sarcoid susceptibility have not yet
been identified, and the incomplete penetrance of this genetic effect suggests
that other as yet undiscovered genes may playa role in the development of
sarcoid tumors.
612 GOODRICH et al

CONSIDERATIONS FOR THERAPY OF EQUINE SARCOID

TUMOR

Sarcoids are treated routinely, and often successfully, by veterinarians in

private practice. Common treatments include benign neglect for small tumors
that do not cause the horse discomfort and do not impede its use, and surgical
excision and various types of immunotherapy for larger sarcoids or those that
impede an animal's use. 12,59 Only limited data on the incidence and prevalence
of sarcoids in the field and on the success of these and other treatments are
available.
Furthermore, it seems likely that the cases of sarcoid tumor referred to large
clinics or hospitals at veterinary schools may not be typical of the overall
population of these tumors. They may represent fast-growing, recurrent, or
multiple tumors that have proven to be refractory to one or more treatments
administered by practitioners. The reports concerning treatment of sarcoids have
most often been generated using cases referred to hospitals or large clinics. The
relevance of these reports to the treatment of primary, and often solitary, sarcoids
is unclear.
Modalities of treatment reported in the literature for equine sarcoids are
diverse. Surgical excision, cryotherapy, excision by carbon dioxide (C0 2 ) laser,
immunotherapy, brachytherapy, hyperthermia, and chemotherapy have all been
used. Few studies have compared more than two types of treatment. No single
approach to therapy has proved universally successful. Choice of and response
to therapy may vary with the mass or number of sarcoids present, the anatomic
location of the sarcoid,28 and the histologic type of the sarcoid (flat, verrucous,
fibroblastic, or mixed).58 Single tumors have a better prognosis than multiple
ones. Prognosis depends on the site and method of treatment. The relationships,
if any, between these variables and response to therapy have not been scientifi-
cally elucidated to date. Choice of therapy is best guided by results of case
studies in which one or Inore types of treatment have been evaluated.1(~,34

Surgical Excision

Studies of recurrence of tumors after surgical eXCISIon are not extensive.

Ragland and colleagues 5R reported that approximately SO°!c> of surgically excised
tumors recurred within 3 years with most regrowths occurring within 6 months
of the surgery, although another group found a 64 % recurrence rate in 14 horses
with sarcoids treated by conventional surgery.16
A guarded prognosis should be given when excision is elected as the
primary treatment for sarcoids. Should tumor regrowth occur, especially in the
immediate postoperative period or shortly thereafter, use of another modality of
therapy (cryotherapy, immunotherapy, brachytherapy, or CO2 laser surgery) in
combination with excision should be considered for the second course of therapy.

Cryotherapy

Cryosurgery alone or in combination with debulking of larger sarcoids

has been employed with some success.olD Approximately 70(j!0 of treated horses
appeared to be free of recurrences in most studies, although rates as high as
100% and as low as 60°!c) have been reported.
Several different cryosurgical systems using liquid nitrogen as the refriger-
 EQUINE SARCOIDS 613

ant are available.:N Currently, the best method of applying the cryogen is by
direct spray.1Y Tumors should be frozen rapidly to at least - 20°C to - 30°C,2°
although even lower temperatures may give better results. It is recommended
that two or three freeze-thaw cycles be completed. In order to control the depth
and degree of freezing, most surgeons advocate the use of thermocouple needles
imbedded in the subcutaneous tissue beneath the tumor and in subcutaneous
tissue beneath presumably normal skin 1 to 2 cm from the periphery of the le-
sion.
Swelling, hyperemia, hemorrhage, and local edema occur after treatment
and treated tissue undergoes necrosis. The average time for healing in one study
was 2.4 months (range, 1.0-3.5 months).h4 Hair follicles are destroyed by freezing,
and the site may thus be hairless initially. New hair is often white. Complications
may be significant if adjacent normal tissue and vital structures are not protected.
Permanent or transient facial nerve paralysis, septic arthritis, loss of the upper
eyelid, and evisceration of the globe have been described. 20 ,39 Freezing cortical
bone may decrease its strength by 70(~).21
Another drawback to cryosurgery for the treatment of sarcoids is the time
required to adequately freeze tumor tissue. In horses with multiple or large
tumors (>3 cm in diameter), it is often impossible to freeze all of the tumor(s)
during one period of general anesthesia.
When only selected sarcoids in horses with multiple sarcoids were subjected
to cryosurgery, spontaneous regression of untreated tumors was occasionally
observed, likely the result of a cryoimmune response to sarcoid cell compo-
nents. 2lJ ,64 These findings, however, were not consistent and need further investi-
gation in relation to multiple tumors and their treatment.

Carbon Dioxide Laser Surgery

A new and promising approach to the treatment of equine sarcoids uses the
CO 2 laser to cut and evaporate tumor tissue. 54, 79 Diehl and colleagues 16 reported
that 81 (Y<:) of 59 horses with sarcoids treated by CO 2 laser were free from recur-
rence after 12 months. In the same study, 60°/<) of 35 horses in which sarcoids
were treated by cryosurgery and 64(% of 14 horses in which sarcoids were treated
by conventional surgery were sarcoid-free after 12 months.
Carstanjen and colleagues 14 reported on recurrence of sarcoids in 60 equidae
(horses, donkeys, mules, ponies) that had been treated by CO 2 laser at least 6
months prior to re-evaluation. Recurrence was observed in 23 animals (38(~0
recurrence rate). Some of these wounds (13%) were vaporized, 48°!c) were re-
sected, and 39<X) were resected and the wound edges were either opposed or the
surgical wound had a synthetic skin substitute applied. In this study, it was
found that animals with multiple sarcoids were more predisposed to recurrence
and that donkeys showed a significantly lower recurrence rate than horses.
After CO 2 laser resection and evaporation of tissue, the surgical site is dry
and clean. Swelling usually does not occur, and the surgical wound is not
painful to palpation. If enough normal skin is available, a primary closure can
be made over the site. 79 When the site is left open, healing by second intention
without hypergranulation occurs. Epithelialization and wound contraction may
be slow.'16
Certain safety precautions must be taken when using the CO 2 laser, includ-
ing use of a smoke evacuator to eliminate laser plume, as there is danger of
explosion. 54 The extent to which the plume may be dangerous remains to be
determined, but careful use of an efficient smoke evacuator is imperative.
614 GOODRICH et al

The CO2 laser appears to be a highly reliable method of treating equine

sarcoids. Unfortunately, the equipment needed is expensive, its operation re-
quires specialized training, and expert technical assistance is necessary to keep
the unit running safely and efficiently. These problems currently limit the use of
CO2 lasers to universities and a few specialized private practices.

Immunotherapy

Treatments for equine sarcoids with an immunologic basis have been widely
applied. 33, 59, hi Bacillus of Calmette and Guerin (BCG), an attenuated strain of
Mycobacteriun1 bovis, is an immunomodulator and is the agent most commonly
employed for immunotherapy of equine sarcoids. Live organisms, killed bacilli,
or cell wall extracts 6 have been combined with various adjuvants for intralesional
injection in sarcoids as well as in some tumors in human beings. The mechanism
of action of BCG is not entirely clear. Critical prerequisites for successful BeG
therapy are a limited tumor burden, immunocompetence of the host, an ade-
quate dose of BCG, and close association of BCG and tumor cells. BCG may
somehow stimulate the host's immune system to recognize sarcoid cells as
foreign. Sarcoid tumors are poorly antigenic, and the host antisarcoid immune
response has been difficult to demonstrate in naturally occurring disease (re-
viewed by Gorman 24 ). Mycobacterial antigens stimulate host lymphocytes and
may also stimulate an increase in natural killer cells. 6 , 41, 78 Histopathologic
evaluation of treated regressing sarcoids showed that only sarcoid cells (and not
the surrounding normal cells) underwent necrosis.78 BCG may thus induce a
tumor-specific immunity.
Response to immunotherapy appears to depend on the anatomic location
of the sarcoid, the size of the tumor, the number of tumors present, and perhaps
the tumor type. Periocular sarcoids are the most uniformly responsive to immu-
notherapy. With intralesional BCG injection, Steiner64 obtained an 83.5°1<) (10 of
12) rate of remission of periocular sarcoids but only a 48.5<Yo rate of remission
from all other body regions. Sarcoids on the legs and in the axillary region
respond especially poorly to immunotherapy.53
Local response to intralesional BCG injection may be dramatic, especially
after two or more injections. Swelling occurs within minutes or hours and may
be extensive. Inflammation progresses to necrosis and ulceration of the tumor;
fever (40°C [104°P] in some patients), increased white blood cell count, and
general malaise also occur in some cases. 3 -l Complete resolution of the process
and tumor regression takes from 6 weeks to 1 year or more, with many patients
requiring months for resolution to occur. 34, 41, 64, 78
BCG therapy is not without risk. Complications can include death from
anaphylactic shock after two or more injections. Therefore, premedication with
flunixin meglumine and corticosteroids has been recommended.78 , H4 Intralesional
BCG injections have also been associated with nonfatal anaphylaxis,3H severe
local inflammatory reactions (including lymphangitis),3-l and septic arthritis. 53
Anaphylactic reactions should be less frequently associated with the use of
vaccines containing mycobacterial cell wall fractions, which may be virtually
protein-free, than with the use of whole-organism vaccines. 53
Intralesional BCG therapy appears to have a place in the treatment of equine
sarcoids, especially those in the periocular region. This modality of therapy is
practical, because expensive equipment and a hospital environment are not
required for its use and the cost is not prohibitive. The client should be apprised
of the risks of therapy, especially when tumors are located on the extremities.
 EQUINE SARCOIDS 615

Immunotherapy is likely to fail when multiple or large tumors are present.

Debulking of all but the smallest sarcoids is advised prior to injecting BCG
intralesionall y.
More recently, other types of nonspecific immunotherapy have been used
to treat sarcoids. Although many veterinarians believe these treatments to be
beneficial, adequate controlled trials have not been conducted for ll10st prepara-
tions. In one controlled trial, a high rate of sarcoid remission in the placebo
group was reported, suggesting caution in the application of nonspecific immu-
nomodulators. h5
A new technique for specific immunotherapy has been described recently.6H
This procedure uses autologous polymerized tumor tissue combined with tuber-
culin purified protein derivative as an adjuvant. The results reported in a group
of nine horses, including five that had been treated unsuccessfully previously
by other methods, were encouraging.

Interstitial Brachytherapy

Various isotopes have been used for interstitial brachytherapy of equine

sarcoids and other fibrous connective tissue sarcomas: permanently implanted
seeds of radon-222 or gold-198; removable needles of radium-226, cobalt-60, or
iridium-192; and ]92Ir seeds using an afterloading technique.76 Response to tumor
treatment ranged from 50% to 100%. Turrel and Koblik 75 reported that 95°;{) of
periorbital sarcoid-affected horses treated with 192Ir interstitial brachytherapy
had been sarcoid-free for 1 year. At the University of Berne Veterinary Hospital,
brachytherapy is preferred to BCG immunotherapy for tumors around the eyes,
as there are few side effects.
The principal advantage of brachytherapy is the continuous delivery of a
high dose of radiation locally to the tumor while sparing adjacent healthy tissue.
Placement of the implants results in radiation exposure for the surgeon, however.
This is minimized in the afterloading technique. In some procedures, special
equipment may be necessary. The horse must be maintained in a radiation
safety-approved area, and the cost may be significant depending on the size of
the tumor. Interstitial brachytherapy may be combined with surgical debulking
of large tumors to decrease the cost of the implants and improve chances for
success. Hyperthermia and radiation therapy may be combined, because these
two modalities of treatment have synergistic effects on the killing of tumor
cells. 76
For recurrent, aggressive, and surgically inaccessible sarcoids, brachyther-
apy should be considered. The size of the tumor limits its application.

Hyperthermia

Radiofrequency current-induced hyperthermia has been reported to induce

regression with no recurrence at 7 to 12 months after the last treatment in three
cases of sarcoid tumors. 27 The tumor tissue was heated to 50°C for 30 seconds
with a 2-MHz radiofrequency current. The procedure was repeated at intervals
of 1 to several weeks. Hyperthermia may be synergistic with radiotherapy in
killing tumor cells.7h Because of its limited reported use thus far, the true efficacy
of hyperthermia is unclear, and this procedure needs further testing.
616 GOODRICH et al

Chemotherapy

Daily topical applications of caustic or antimetabolite drugs such as podo-

phyllum47 and 5-fluorouracil have been advocated for the treatment of small
sarcoids.7' 8, 77 Results of topical chemotherapy have been inconsistent, however,
and only a few published studies are available for reference.
The most recent and perhaps the most promising chemotherapeutic treat-
ment available today is the drug cisplatin (Platinol; Bristol Myers Squibb,
Princeton, NJ, [1-800-437-0994]). Theon and colleagues 73 evaluated intratumoral
treatments of cisplatin in 19 horses with sarcoids and found that at 1 year, 87%
of the horses were relapse-free. In another study by the same group/l 27 horses
(32 lesions) were treated with surgical debulking or excision combined with
perisurgical wound injection of cisplatin and sesame oil injections. Relapse-free
survival rates were 92% at 1 year and 77°!c) at 4 years. The local wound toxicosis
was found to be minimal and did not appear to affect wound healing. These
two studies have provided optimistic results for the treatment of sarcoids in
which the therapy is practical, relatively safe, and available both to the private
practitioner and to referral institutions.

SUMMARY OF TREATMENT OPTIONS

To the veterinarian who wishes to consider all the potential treatment

options and choose the optimal therapeutic course for his or her patient, the
menu of possibilities may become confusing. The factors that should be consid-
ered in the treatment of equine sarcoids include availability of treatment, location
of tumor(s), cosmetic considerations, cost of treatment, potential complications,
and the risks of therapy to both the patient and the owner.

Availability of Treatment

Depending on the site and extent of the lesion, surgical excision of sarcoids
can be perforlned in the field or in the hospital; usually, no more than a biopsy
kit and suture material are required even if the wound requires closing. Most
referral institutions and many practitioners also have a cryosurgical system and
a small liquid nitrogen container which may be easily transported for field
procedures.
Products that contain an attenuated strain of M. bovis or killed bacilli or cell
wall extracts are easily obtained from pharmaceutical companies and are avail-
able to any practitioner who can write prescriptions.
Most chemotherapeutic agents are also available to practitioners. At this
time, Platinol is available to private practitioners as well as to clinicians at
academic institutions. Cisplatin can be purchased as a lyophilized powder or as
an aqueous preparation (Platinol-aq). The aqueous formulation results in lower
concentrations within the tissues and may not be as efficacious. 5-Fluorouracil
(Adrucil, Florida Infusion, Palm Harbor, FL, [1-800-624-0152]) may be obtained
by both academic institutions and private practitioners. Fewer reports exist on
treatment with 5-fluorouracil; therefore, its efficacy is not as well established as
that of cisplatin.
The CO2 laser is expensive to obtain and costly to maintain; therefore, it is
found in only a few private practices. These instruments are available at some
academic institutions and a few referral clinics, however. Interstitial brachyther-
 EQUINE SARCOIDS 617

apy is even more rare because of its high cost and the difficulty in obtaining
licenses. A telephone call to your local referral sites should determine which of
these treatments options may be available.

Location of Tumor

When considering treatment of sarcoids, tumor location often determines

how the lesion should be managed. As previously mentioned in this article,
periocular tumors are often difficult to surgically remove, debulk, or freeze due
to the risk of damaging important ocular structures (see the article on treatment
of periocular tumors in this issue). Nevertheless, good success has been achieved
with immunotherapy, chemotherapy, and interstitial brachytherapy.59, 73
Tumors on the trunk and upper limbs may be amenable to surgical excision
or debulking using sharp transection or the CO2 laser combined with perilesional
chemotherapy because of the greater availability of loose skin?"78 Cryotherapy
is also a viable option for tumors located in these areas. General anesthesia
or sedation and local anesthesia are used with these procedures. Interstitial
brachytherapy is also an alternative course for the larger, perhaps recurrent,
tumors in these locations.
Tumors located midlimb or distally can present the clinician with the chal-
lenge of removing the maximum amount of neoplastic tissue without damaging
or invading important vascular, bony, or synovial structures. In our experience,
tumor treatment works best when debulking is performed cautiously and com-
bined with multiple treatments of the cisplatin and sesame oil combination.
Caution should be used when applying cryotherapy for tumors in these loca-
tions, because it is difficult to know the exact depth to which the tissue has
been frozen.

Cosmetic Considerations

Surgical excision combined with perilesional chemotherapy may allow a

good cosmetic result if the skin can be opposed. As reported, wound healing
does not appear to be affected by cisplatin and sesame oil injections. 71 Total
excision of the tumor must not be compromised in order to obtain a superior
cosmetic result, as this may lead to regrowth of the tumor. In our experience, 5-
fluorouracil treatment seems to have a similar cosmetic outcome to cisplatin
injections. If complete tumor excision can be accomplished with wide margins,
wound surfaces may be grafted. One report described three horses in which
sarcoids were removed and the sites immediately skin grafted using a derma-
tome. H3 In all three horses, good cosmetic results were achieved.
When surgical excision is used with a CO 2 laser, a brownish yellow surface
results which is often dry and hard. When these skin surfaces are left to
epithelialize or are subjected to perilesional chemotherapy injections, the cos-
metic results seem to be superior to those resulting from sharp transection, and
the occurrence of hypergranulation tissue may be reduced.
Cryotherapy often leaves an area of tissue scarring due to destruction of
hair follicles and affected tissues. Hair regrowth most often is white, and if the
tumor is on or near an important structure such as the eyelid, that structure
may be damaged or become dysfunctional if the treatment extends inadvertently
to the associated nerves and muscles.
Immunotherapy may also leave scarring, with tissue sloughing and exudate
618 GOODRICH et al

throughout the period of tumoral injection. The cosn1etic outcome depends on

the area of tissue injected and nUlnber of treatn1ents required.
Intralesional brachytherapy may result in permanent epilation or regrowth
of hair that is white. This also is dependent on the alnount of tissue that needs
to be treated.

Cost

The cost of treating sarcoids varies greatly and is determined by many

factors, including the number of tumors present, size, location, choice of therapy,
and whether general anesthesia or sedation combined with local anesthesia is
required. Perhaps the most important factor is whether or not the tumor recurs
and therefore requires additional treatments.
At the Large Animal Clinic at Cornell University, the cost of cryotherapy is
approximately $100 to $150 per treatment for tumors that are between 3 and 6
cm in diameter. This does not include cost of sedation combined with local
anesthesia or general anesthesia. Although this treatment may seem to be expen-
sive, most tumors are treated only once, and the recurrence rate is low.
Treatment with the CO 2 laser may also involve surgical debulking or exci-
sion. Treatment of tumors that are 3 to 6 cm in diameter, and perhaps invasive,
can range in cost from $100 to $200 and higher.
The cost of immunotherapy depends in large measure on where the prod-
ucts are purchased and the amount needed for treatment. Currently, the product
Nomagen-V M. bovis can be purchased from Vetrepharm Research, Athens,
Georgia for $50 per vial. At least four to five treatments should be considered
when estimating costs for the client.
Platinol can be purchased from Bristol Myers Squibb for $34 per vial (see
section on availability). Each vial has 10 mg of lyophilized powder. Each cubic
centimeter of tumor should be treated with 1 mg of drug?l Platinol-aq comes in
50-mg vials (1 mg/mL), and the cost is $135 per vial. 5-Fluorouracil (Adrucil) is
available in 500-mg vials, where 10 vials (10 mL per vial) are in one box and
each box costs $13.50. Adrucil is also available in 5-g vials at the cost of $14.50
per vial. In estimating costs for chemotherapy, multiple treahnents need to be
factored into total costs.
Interstitial brachytherapy can be very expensive due to the need for hospi-
talization and to the cost of the treatment itself. Costs vary depending on types
and numbers of implants used and the period of hospitalization required.

Risks and Complications

Perhaps the most con1mon complication of treating sarcoids is tumor re-

growth. This complication is dealt with best by ren10ving the maximum amount
of affected tissue possible without damaging in1portant structures and compro-
mising anatomical function. Debulking is almost always combined with other
modes of therapy to ensure that the possibilities of regrowth are minimized. The
risks of treatment to both the patient and the owner must be weighed against
the efficacy of treatment. A complication of surgical debridement and reapposi-
tion of skin edges may be incisional dehiscence. This risk is not increased with
injections of cisplatin and sesame oil, however; therefore, these two treatments
may be combined?!
In the report by Theon et aFl on intratumoral injections of cisplatin, one
 EQUINE SARCOIDS 619

horse developed a clostridial infection which ultimately resulted in death. Pre-

cautions, including peri-injectional antibiotics and careful aseptic lesion prepara-
tion, should be practiced. Some degree of tissue sloughing and perilesional
swelling may be expected. In all reports of intratumoral injections of cisplatin,
local toxicosis was minimal, however.7 1- 71
Although there are only few reports on the use of 5-fluorouracil in treating
sarcoids, one report in which squamous cell carcinoma lesions were injected
reported minimal tissue toxicosis.]l)
Although it is now relatively easy for licensed veterinarians to obtain
chemotherapeutic drugs, great care should be taken to minimize exposure to the
client and to the veterinarian injecting the drug. At the Large Animal Clinic at
Cornell University, the veterinarian injecting the drug wears a disposable surgi-
cal gown, latex gloves, protective eyeware, and a surgical mask and hat to
minimize exposure. Any assistants holding or restraining do the same, and the
client is not allowed to hold the animal. Furthermore, luerlock syringes and
extension sets are used for injecting to minimize the risk of the pieces becoming
disconnected while under pressure and contaminating other surfaces. Following
injections, all material is placed in biohazard containers.
Local responses to immunotherapy can be severe and can progress to
systemic signs in some cases. 14 Anaphylaxis has also been reported,3R and clients
should be forewarned of this possibility.
Interstitial brachytherapy has a risk of exposure of the materials to the
client; therefore, most cases are isolated in special facilities until removal of the
implants. The greatest risk is to the surgeon implanting the material, and few
complications associated with the patient have been reported.

CONCLUSIONS

Sarcoid tumor remains an important clinical entity in equine medicine and

is numerically, at least, the most significant equine tumor. Many questions
remain concerning the etiology and pathogenesis of sarcoids. If sarcoids are
caused by a BPV, how is the virus transmitted and why is the incidence so low?
Why are there so many forms of sarcoid tumors and why is their response to
treatment so variable?
Fortunately for the equine clinician, most cases of sarcoid tumors are treated
successfully without the need for referral to secondary care centers, and new
forms of chemo- and immunotherapy hold promise for improved success in the
future. Sadly, little information is available on the incidence or prevalence of
sarcoids in the field, however. The significant rate of recurrence when many
treatments are used and the recorded examples of spontaneous regression make
objective evaluation of various therapies difficult. Furthermore, few studies have
included a comparison of two or more contemporary treatments.
Nevertheless, the many facets of the biology of the equine sarcoid tumor
make it a fascinating entity for further investigation in veterinary medicine and
an equine neoplasm with an infectious origin that practitioners can successfully
treat.

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Address reprint requests to

D. F. Antczak, VMD, PhD
James A. Baker Institute for Animal Health
College of Veterinary Medicine
Cornell University
Ithaca, NY 14853