Case Report
Carboplatin for treatment of a Sertoli cell
Keywords
avian, cancer,
chemotherapy, germ cell
tumor
Correspondence address:
Kenneth M. Rassnick
Cornell University, College
of Veterinary Medicine
Box 31, Ithaca, NY 14853,
USA
e-mail: kmr32@cornell.edu
tumor in a mallard (Anas platyrhynchos)
S. E. Childs-Sanford1, K. M. Rassnick2 and A. Alcaraz3
1
Section of Wildlife Health, Department of Clinical Sciences, Cornell University, College of Veterinary
Medicine, Ithaca, NY, USA
2
Sprecher Institute for Comparative Cancer Research, Department of Clinical Sciences, Cornell University,
College of Veterinary Medicine, Ithaca, NY, USA
3
Department of Biomedical Sciences, Cornell University, College of Veterinary Medicine, Ithaca, NY, USA
Abstract
A 13-year-old male mallard was diagnosed with a non-resectable Sertoli cell tumor involving the
left testis. The duck was treated with four doses of single-agent carboplatin given at 4- to 5-week
intervals. Heteropenia, 2 weeks after each treatment, was the acute dose-limiting toxicity. The
tumor reduced in size by 25%, and the duck’s clinical condition improved for 12 months. Sertoli cell
tumors are rare in birds, and this is the first report, to our knowledge, of attempted chemotherapy
treatment in the veterinary literature.
Case report Physical examination findings at Cornell
University revealed the duck to be approximately
A 13-year-old 1.1-kg male mallard was referred to
5% dehydrated and in thin body condition. The
the Zoological Medicine Service of the Cornell
coelomic mass could not be palpated through the
University Hospital for Animals for the evaluation
abdominal window. The remainder of the physical
of a coelomic mass. Approximately 2 weeks before
examination was unremarkable other than mild
presentation, the duck was examined by a referring
tachypnoea with normal respiratory effort. A
veterinarian for a 1-month history of inappetence,
complete blood count (CBC), plasma bio-
tachypnoea, reluctance or inability to fly and
chemical profile, faecal flotation, plasma protein
lethargy. Whole-body radiographs performed at
electrophoresis, serum Aspergillus antibody titre
that time demonstrated a large mass in the mid-
(Minnesota Raptor Center, St Paul, MN, USA),
dorsal coelomic cavity. Bacterial pharyngitis was sus-
whole-body radiographs and coelomic ultrasound
pected, and enrofloxacin (15 mg/kg orally once
were performed. Results of the CBC, plasma bio-
daily) was prescribed. The owner, a wildlife rehabili-
chemical profile and protein electrophoresis were
tator, initiated daily tube feeding with Oxbow herbi-
unremarkable, and the faeces were negative for
vore critical care diet (Oxbow Enterprises, Murdock,
parasites. The Aspergillus antibody titre was nega-
NE, USA). The mallard was obtained as a duckling
tive. A faecal gram stain showed a normal bacterial
and was not releasable because of imprinting on
flora with occasional non-budding yeast and a
humans. The duck’s housing included both indoor
few sporulating gram-positive rods (suspected
and outdoor access, and its normal diet consisted
Clostridium spp.). Whole-body radiographs con-
primarily of poultry pellets mixed with cracked corn.
firmed the presence of a round, 4.8-cm diameter,
well-defined mass in the mid-dorsal coelomic cav-
Present address: S. E. Childs-Sanford, 137 Brook Way,
Ithaca, NY 14850, USA. ity (Fig. 1). Coelomic ultrasonography revealed a
ª 2006 The Authors. Journal compilation ª 2006 Blackwell Publishing Ltd 51
52 S. E. Childs-Sanford et al.
Figure 1. Right lateral radiograph of an adult male mal-
lard with a large coelomic mass (arrows).
smooth-margined coelomic mass with a heteroge-
neous echogenicity. The origin of the mass could
not be determined from the ultrasonic examina-
tion. Coelomic fluid was not identified, and the
remaining coelomic organs appeared normal.
The duck was premedicated with butorphanol
(1 mg/kg) and midazolam (0.2 mg/kg) given
intramuscularly and placed under general anaes-
thesia with isoflurane. A coelomic exploratory,
performed using a ventral midline approach
with bilateral cranial horizontal flaps, revealed a
cream-coloured mass dorsal to both the ventricu-
lus and liver and slightly cranioventral to the left
kidney. The mass was firm, smooth and highly
vascular. It was attached to the dorsal body wall
by a short stalk in which at least one large arterial
vessel was palpable. Due to the inability to visua-
lize the origins of these vessels before dissection
and ligation, even with the use of intraoperative
rigid endoscopy, it was concluded that the mass
could not be safely resected. Multiple incisional
biopsies were performed and immediately fixed in
10% neutral buffered formalin. The duck made an
uneventful recovery and was discharged from the
hospital 2 days later. Histopathological examina-
tion of the mass biopsies was consistent with a
Sertoli cell tumor (Fig. 2).
The duck was re-examined 4 weeks postopera-
tively. The surgical incision had healed, and the
duck’s clinical signs had remained unchanged
from its initial presentation. A second coelomic
exploratory was performed, this time from a left
lateral approach in an attempt to improve visual-
ization of the vascular stalk of the mass and
facilitate removal. There were extensive adhesions
ª 2006 The Authors. Journal compilation ª 2006 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, 4, 1, 51–56
Figure 2. Histological section of a Sertoli cell tumor in a
mallard. The tumor is composed of sheets, irregular rosettes
and irregular tubules of tall, simple to pseudostratified
columnar cells perpendicular to the basement membrane
zone of the tubules. The neoplastic cells have indistinct cell
borders with basally oriented, spindle-shaped, finely stippled
euchromatic nuclei with inconspicuous nucleoli and abun-
dant finely vacuolated, pale eosinophilic cytoplasm. There
were four mitotic figures in 10 high-power fields.
Haematoxylin and eosin, 40 magnification, bar ¼ 20 mm.
of liver and multiple loops of intestine to the
surface of the mass. In some areas, the adhesions
appeared to share blood supply with the mass,
and the mass was considered inoperable.
Three weeks after the second coelomic explora-
tory, the duck was re-examined, plasma uric acid
level was measured, and a CBC and whole-body
radiographs were performed. The CBC and uric
acid levels were unremarkable. Whole-body
radiographs showed persistence of the intra-
coelemic mass, but the margins of the tumor
were indistinct, likely because of the adhesions
that were identified at surgery. Because the
tumor could not be resected, it was decided to
attempt medical treatment with single-agent
carboplatin chemotherapy. A 24-gauge catheter
was aseptically placed in the medial metatarsal
vein. Carboplatin (Paraplatin, Bristol-Myers
Squibb, New York, NY, USA), at a dosage of
15 mg/kg diluted in 25 mL of 5% dextrose, was
administered intravenously over 25 min. There
were no acute adverse effects associated with the
carboplatin infusion. Amoxicillin/clavulinic acid
(125 mg/kg PO q12 h) and itraconazole (5 mg/
kg PO q24 h) were prescribed, and the duck was
discharged from the hospital.
 Sertoli cell tumor in a mallard 53

Carboplatin was administered on three addi- were successfully treated based on culture and anti-
tional occasions, each 5 weeks apart. An initial biotic sensitivity results.
plan to administer carboplatin every 3 weeks was Response to carboplatin chemotherapy was
altered to every 5 weeks when heteropenia was assessed by monitoring whole-body radiographs
noted 2 weeks after the administration of the first immediately before each treatment and then every
carboplatin dose. CBCs were obtained weekly after 12 weeks thereafter. Due to the presence of exten-
the first treatment with carboplatin, uric acid level sive intracoelomic adhesions, the margins of the
was determined, and a CBC was performed imme- Sertoli cell tumor were obscured making radio-
diately before each subsequent treatment. Uric acid graphic interpretation difficult; however, there
levels were all unremarkable. Due to low heterophil was subjectively an approximately 25% decrease
counts postcarboplatin (Fig. 3), the third dosage in the size of the mass by the end of the che-
was reduced by 25%, and the fourth dosage was motherapy course.
further reduced by 25%. Despite the heteropenia There was a very noticeable clinical improve-
that was noted 2 weeks after each of the first three ment in the duck’s condition during the course of
treatments, there were no adverse clinical signs chemotherapy. Beginning 3 weeks following the
observed. Heteropenia was not observed on a CBC first carboplatin injection, it started to eat small
performed 2 weeks following the final carboplatin amounts of food on its own. The duck’s appetite
dose. Thrombocyte and erythrocyte numbers were continued to improve over the next several weeks
not affected during the treatment course. The duck although daily tube feedings with poultry pellet
was maintained on itraconazole (5 mg/kg PO slurry were needed in order for its weight to be
q24 h) throughout the treatment period and until maintained. The duck’s attitude and activity level
approximately 5 months following the final dose of also improved significantly. Following the third
carboplatin. Before discontinuing itraconazole, an dose of carboplatin, it started flying and vocaliz-
Aspergillus antibody titre was repeated, and the ing again. The owner also reported that it seemed
result was negative (Minnesota Raptor Center). to be breathing deeper and slower again, as com-
Periodically during, and less frequently in the pared with the shallower and more rapid breaths
months following the chemotherapy course, the it had shown before starting chemotherapy.
duck experienced mild bouts of bacterial pharyngi- Twelve months after beginning carboplatin
tis as well as clostridial enteritis. These infections chemotherapy, the duck’s clinical condition
began to decline. Its breathing became more
11
3
10 rapid, the owner was unable administer as much
Heterophil count (103/ul)

9
8
2 food during tube feedings, and its voice seemed to
7
6 be more strained and quieter. Whole-body radio-
5 4
4
graphs showed progression of the Sertoli cell
1
3 tumor to nearly twice the original size. Due to
2
1 the poor prognosis and fragile condition of the
0
–3 0 1 2 3 4 5 7 10 12 14 16 duck, a second course of carboplatin was not
Week of treatment
recommended, and the owner elected to continue
Figure 3. Graph representing the carboplatin treatments supportive care at home. The duck’s condition
and heterophil counts in a duck with unilateral Sertoli cell continued to deteriorate, and it died at home
tumor. The first (1) and second (2) doses of carboplatin 1 month later. A necropsy was not performed.
were administered intravenously at a dosage of 15 mg/kg,
the third (3) was administered at 12.5 mg/kg, and the
fourth (4) was administered at 8.5 mg/kg. The heterophil Discussion
count reference range for a mallard is 6.04  4.678 
103 mL1 (International Species Information System, 2002),
Primary germ cell testicular tumors, including
and heteropenia was observed after the first Sertoli cell tumors, are rare in birds. Reports of
(1.28  103 mL), second (0.84  103 mL1) and third testicular tumors are most prevalent in caged
(0.72  103 mL1) carboplatin doses, respectively. psittacine birds, especially budgerigars.1,2 Sertoli

ª 2006 The Authors. Journal compilation ª 2006 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, 4, 1, 51–56
54 S. E. Childs-Sanford et al.
cell tumors have also been reported in a brown
leghorn capon,3 Japanese quail4 and a weaver
bird.5 A Sertoli cell tumor in a Gouldian finch
was thought to be associated with avian polyoma-
virus.6 Bilateral seminomas have been reported in
a mallard,7 but the present case report is, to our
knowledge, the first documentation of a Sertoli
cell tumor in a duck.
Cryptorchidism is an important risk factor for
the development of testicular neoplasia in both
humans and domestic dogs.8–10 The retention of
testes within the abdominal cavity is normal for
some species, however, including testicondid
mammals and all avian species, and does not
appear to result in an increased risk of testicular
cancer. In humans, testicular tumors typically
have an aggressive biological behaviour, although
in dogs, few (<10%) of these tumors metasta-
size.11,12 Metastases to the liver, kidney, spleen,
adrenal gland, pancreas and lung have been
reported in dogs,13 but potential metastatic sites
in birds have yet to be reported. In this case, there
was no evidence of metastasis at the time of either
exploratory surgery; however, it is unknown
whether metastasis occurred late in the course of
the disease because a necropsy and histopatholo-
gical evaluation of all tissues were not available at
the time of the duck’s death. Clinical signs con-
sistent with feminization secondary to hyperestro-
genemia from functional Sertoli cell and other
germ cell testicular tumors have been reported
in both mammalian and avian species.3,14–16
Changes that have been observed in birds include
a change in colour of the cere (blue to brown),
polyostotic hyperostosis, pancytopenia and the
development of female plumage characteristics.
No clinical signs implying hyperestrogenemia or
feminization were observed in the duck in this
case.
Due to the high sensitivity of testicular germ
cell tumors to cytotoxic treatment as well as
concentration of these drugs within the testis,
platinum-based chemotherapeutics are known
for their good efficacy when used for the treat-
ment of testicular cancer in both humans and
dogs.11,17–20 The results of a study on the phar-
macokinetics of carboplatin in sulphur-crested
cockatoos demonstrated variable levels of
ª 2006 The Authors. Journal compilation ª 2006 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, 4, 1, 51–56
platinum accumulation in the testes; however,
this was considered to be due to the fact that
two birds in the small sample size had immature
gonads.21 In people with germ cell tumors, multi-
ple randomized clinical trials have compared out-
come following treatment with cisplatin or
carboplatin, and data confirm that cisplatin is
superior.22 Both cisplatin23 and carboplatin21
have been evaluated in normal birds, but a safe
dosage and diuresis protocol for cisplatin have
not been reported. A lower dosage of carboplatin
than that reported herein (5 versus 15 mg/kg) was
used to explore the pharmacokinetic disposition
in normal cockatoos.23 Based on that study and
preliminary unpublished observations by one of
the authors (Filippich) 15 mg/kg appeared to be a
safe starting dosage for use in the duck in the
current case report. Reavill et al.24 reported treat-
ment of a germ cell tumor in a cockatiel with
carboplatin at 5 mg/kg every 3 weeks, but the
exact nature of the tumor and the duration of
treatment were unclear.
To the authors’ knowledge, this is the first
report of attempted chemotherapy treatment for
a non-resectable Sertoli cell tumor in a duck.
When assessing response to chemotherapy, most
investigators define ‘remission’ as 50% reduc-
tion in tumor burden.25 The Sertoli cell tumor in
the duck reported herein was reduced in size by
approximately 25% after treatment; however,
numerous adhesions prevented accurate measure-
ments. This reduction in tumor size was consid-
ered highly significant for the duck, however,
because its quality of life (attitude, activity level
and appetite) improved after treatment, and these
benefits persisted for more than 8 months follow-
ing the completion of therapy.
Due to the high susceptibility of waterfowl to
aspergillosis, the duck in this case was monitored
closely for signs of infection including an abnor-
mal antibody titre, an elevated white blood cell
count and clinical signs of respiratory compro-
mise. This condition typically occurs secondary to
other concurrent disease conditions or immuno-
suppression, and thus, this duck was considered
to be at high risk for this disease. The use of
itraconazole throughout the chemotherapy period
appeared to be an adequate preventative measure,

as the duck showed no signs of infection and
retained a negative antibody titre and normal
white blood cell count prior to cessation of this
anti-fungal drug.
The dose-limiting toxic effect of carboplatin in
humans, dogs and cats is bone marrow suppres-
sion.26–28 This may also be the case in avian spe-
cies, as myelosuppression was the major clinical
adverse effect in this mallard. Carboplatin is
excreted primarily by the kidney via glomerular
filtration and myelosuppression in humans29 and
cats28 and has been be correlated with an indivi-
dual patient’s glomerular filtration rate. Plasma
uric acid levels were repeatedly normal in the
duck in this case, but nonetheless, if present, sub-
clinical renal insufficiency may have exacerbated
the haematological toxicity observed. In pharma-
cokinetic studies involving carboplatin in
sulphur-crested cockatoos without neoplasia, a
dose of 5 mg/kg was used and caused mild, tran-
sient gastrointestinal upset.30 Unlike the cocka-
toos, the duck in this case showed no
gastrointestinal side-effects, although the severe
myelosuppression identified approximately
2 weeks after treatment necessitated the reduction
of the third and final doses. The duck was thought
to have been predisposed to recurrent pharyngitis
because of the trauma associated with daily tube
feedings and was likely more prone to these infec-
tions during chemotherapy because of the inter-
mittent heteropenia. Significant heteropenia was
observed at 2 weeks following each of the first
three carboplatin doses, but not at 2 weeks after
the final carboplatin dose. Because further sam-
pling was not performed, the heterophil nadir
following the final dose may have been missed,
or perhaps the reduced dosage (8.5 mg/kg) may
avoid the side-effect of myelosuppression in this
species. Although thrombocytopenia can be a
common side-effect of carboplatin chemotherapy
in mammals,29,31 the absence of an effect in this
duck may be due in part to the difference in
origin of thrombocytes in the duck (mononuclear
precursor) as compared with mammals (multi-
nucleated megakaryocytes).32 The maximum-tol-
erated dose of carboplatin in birds is not known,
and true species-specific dose-escalating studies
are needed. Furthermore, it is not known whether
ª 2006 The Authors. Journal compilation ª 2006 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, 4, 1, 51–56
Sertoli cell tumor in a mallard 55
the duck reported herein was showing cumulative
bone marrow damage after each treatment with
carboplatin. In humans, separate carboplatin dos-
ing formulae are necessary for patients previously
exposed to myelosuppressive therapy.33 Bone
marrow cytology or information obtained from
necropsy may have proven useful to address this
question. Additional studies involving more birds
given multiple administrations of carboplatin are
required.
In summary, germ cell tumors are rare in birds,
and there has been no previous report of a non-
resectable Sertoli cell tumor in a mallard.
Treatment with carboplatin reduced the tumor
size and improved the duck’s clinical condition
for approximately 1 year. Further studies to eval-
uate the efficacy and toxicity of chemotherapeu-
tics in birds are warranted.
Acknowledgments
The authors thank Dr Holly Reid for referring this
patient and providing bloodwork results, Drs Michele
Steffey, Ricardo DeMatos and Seth Nydam for assis-
tance with surgical and case management, Dr Lucio
Filippich for advice and recommendations pertaining
to the chemotherapy treatments and Dr George Kollias
for his editorial input.
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