Histopathologic Features and Post-surgical Sequelae

Veterinary Pathology Online
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Histopathologic Features and Post-surgical Sequelae of 57 Cutaneous Neoplasms in Ferrets ( Mustela
putorius furo .)
G. A. Parker and C. A. Picut
Vet Pathol 1993 30: 499
DOI: 10.1177/030098589303000602
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Vet Pathol 30:499-504 (1993)
Histopathologic Features and Post-surgical Sequelae of
57 Cutaneous Neoplasms in Ferrets
(Mustela putorius furo L.)
G. A. P A R K ER AND C. A. P ICU T
Biotechnics, Sterling, VA
Abstract, The study o f the signalme nt, histomorphologic features, and po st -surgical clinical progress of 57
cutaneous neo plasms in 55 domes tic ferrets (Mustela put orius I ura L.) was based on diagnostic path ologic
ac cessions ( 198 7-1 992) fro m 142 ferrets. Mea n age of th e gro up was 4.3 years; 3 1/54 (57 %) were female and
23/ 54 (43%) were ma le, T hirt y-three (58%) of the cuta neous neoplas ms were bas al cel l tumors. T he mean age
o f ferrets wit h ba sal cell tumor wa s 5.2 yea rs, a nd 23 /33 (70%) were female. Hi stologica lly, th e ba sal ce ll tu m o rs
were co m posed of well-differentiated basaloid epithelia l ce lls with vario us degrees of sq uamous and sebaceous
differentiation , sim ila r to those see n in basal ce ll neoplasms ofdogs. Nine ofth e 57 (16%) cuta neous neo plasm s
were mastocytomas. The mean age of ferret s with mastocytoma was 4.1 yea rs; four were male, four were fem ale,
a nd th e sex ofo ne wa s unrecorded . Hi st ologicall y, th e mastocytomas were composed of well-differentiated mast
ce lls with few cosino phils, similar to cuta neous mastocytomas of domestic cats. The mast ce lls had a small
num ber o f metachromatic cyto plas m ic gra nules, and in six of eight neoplasm s th e gra nules had an affinity for
co nj uga ted avidin-peroxidase. Six o f th e cutaneous neoplasms (II %) were fibromas. The mean age of ferret s
wi th fi bro m a was 2.7 yea rs; 5 (83(\10) were male. Two cu taneo us heman giomas (4%) were in fem a les, which were
4 and 5 years of age. There was o ne each hemangiosarcoma, cutaneo us po lyp, ana l gland ad enocarcinoma,
lym ph osarco ma of th e pre puce and inguinal lymph node, and adenocarcinoma of the prepuce .
Key words: Bas al ce ll tumor; ferrets; fibroma; fibrosarcoma; mastocytoma; neoplasia; spontaneo us disease.
The ferret (Mustela spp.) is generally recognized as
a low tumor incidence species.'? Th e most commonly
reported tumors are lym ph osarcoma and ovarian neoplasms,
although the incidence ofovarian neoplasms
is strongly influenced by the report of 20 ovarian leiomyo
mas in a single colony of ferrets." Cutaneous neoplasms
arc the th ird most commonly reported neoplasms.
A review ofpublished reports an d unp ublished
case reco rds from 16 diagnostic laborat ories revealed
161 neoplasms in ferrets , 30 of which were located in
the skin or subcutis.'? Published reports of cutaneous
and subcutaneous neoplasms include four ferrets wit h
squamous cell carcinorna.v'

500 Parker and Picut Vet Pathol 30:6, 1993
Table I. T ype and site o f 57 cuta neo us neopl asms in
ferre ts, 8 mon th s to 9 yea rs of age.
Type of
Age
Tumor
Sex*
(ycars r]
Basal cell tumor (n = 33)
Site
I M 6 Head
2 F/s 4 Abdomen
3 F/s 4 Un known
4 M 5 Unkno wn
5 M/ c 5 Lat eral th orax
6 M 6.5 Hock
7 F/s 4 Behind car
8 F 2 Mammary region
9 F/s 6 Front leg
10 F 6.5 Foot
II M/c 5 U nkno wn
12 F/s 5 Ingu inal area
13 M 5 Unkno wn
14 F/s 6 Tarsal region
15 F 6 Tail
16 F/s 5 Dorsal th orax
17 F 5 Ventral neck
18 F 3 Dorsal ca rpus
19 M U U nkno wn
20 F/ s 7 Front leg
2 1 F/s 5 Sho ulde r
22 F 4 Ventral neck
23 M/ c 5 Dorsal sacrum
24 F/s 6 Unkno wn
25 F 5 Head
26 M/ c 3 U nk no wn
27 F 3.5 Rear foot
28 F 8 Beh ind ea r
29 M 9 Shoul der
30 F/s 5 Thigh
31 F 6.5 Back
32 F 6 Head
33 F/s 4 Foot
Mastocytoma (n = 9)
34 M/c U Flank/ear
35 U U Foot
36 F/s 3 Fo releg
37 F/s 5 U nknown
38 F/s 3 Base of ear
39 M/ c 6 Brachium
40 M 6 Neck
41 M 3 Hip
42 F 3 Base of tail
Fibroma (n = 6)
43 M/ c 3 Do rsum
44 F I Ventral neck
45 M 3.5 Ax illa
46 M 3.5 U ns peci fied
47 M 4. 5 Neck
48 M 0.8 Thorax
Type of
Tumor
Sex*
Fibrosarco ma (n = 2)
49 M
50 F
Hem an gioma (n = 2)
5 1:j: F/s
52§ F/s
Heman gio sarcoma (n = I)
Table I. Co ntinued.
Age
(ycars)]:
U
4
5
4
53 F U
Apocrine gland ade nocarci no ma (n = 2)
Lumbar
Pin na
Site
Sh oulder
Abdo me n
Lip co mmissure
54 M/ c 7 Anal gland
55 M 6 Prepuce
Lymphosarcom a (n = I)
56 M 6
Cutaneo us polyp (n = I)
57 F 5
Prepuce
Metatarsu s
* F/s = female, spayed; M/c = male, castrated; U = unknown.
t U = unknown.
t Same animal as No. 30.
§ Same animal as No. 42.
were inc ubated in 3% hyd rogen pero xide (Fishe r Scienti fic,
Fa ir Law n, NJ) in methan ol for 10 minutes at 23 C and
washed in PBS. Sections were inc ubated with a I : 10 d iluti on
of avidin-peroxid ase (Zy med Lab orat ories, San Fra ncisco ,
CAl for 25 minutes at 23 C and rinsed in PBS. T o dem on ­
stra te peroxidase, 3% hyd rogen per oxid e and ami noethylca
rbazo le (AEC) (Zym ed Lab orat ories, San Francisco , CAl
were added. Secti on s were rinsed in d istill ed wat er and co unterstained
with G ill's II hem at oxylin (Surgipa th, R ichmond,
IL). Sections of a ca ni ne mastocytoma served as a posit ive
control. Negati ve co ntro l consisted ofsections ofcanine an d
ferret mastocytoma treated with hydrogen peroxide-AEC.
Fig.I. Skin; tumor No. I. Exo phy tic cutaneous basal cell
tumor in a ferret. HE. Bar = 35 mm.
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Vet Path ol 30:6. 1993 Skin T umors in Ferre ts 501
Fig. 2. Skin; tum or No . I. Cutaneous basal cell tu mor with centrilobular sebaceous di fferen tiat ion in a ferre t. Mitotic
figures arc present. HE. Bar = 30 11m .
Fig. 3. Skin; tumor No . 30. Cutaneous basal cell tumor with areas of squamous differentiation (arrows) in a ferret. HE.
Bar = 30 11m .
Basal cell tumor
Results
Th irt y-three of 57 (58%) cutaneo us neopl asm s in
ferrets were classi fied as " basa l cell tumors," acco rdi ng
to diagnos tic criteria applied to th ose of dom estic animals.!?
Age of the 3 1 affected anima ls for who m the
age was known ranged from 2 to 9 years (mean = 5.2
years, med ian = 5 years), and 23 (70.2%) were female.
Site was reco rded in 25 cases : nin e tumors were on the
head , neck, or sho ulders, and nine were on the leg or
foot.
Sixteen of the 33 basal cell tumors were pedunculated
or exo phytic (Fig. I), and the remaining neoplasm
s were plaquelike or endo phytic lesion s. Th e superficial
surface was ulcerated in some cases. All except
one basa l cell tumor had sharply defined borders, and
that exceptio n had on ly minimal invasion of the fibro
us stroma .
T he basal cell neopl asm s consisted of sheets, nests,
and lobules of basa loid epithelial cells. These cells had
a sma ll amo unt of cyto plasm and deeply basophilic,
ro und to ovoid nuclei with indi stin ct nucleoli . Mit oti c
figures were num erou s in some areas of basaloid cells.
All but two of the basa l cell neoplasm s had prom inent
cen tri lobular or multifocal sebaceous di fferentiat ion
(Fig. 2), and all had some degree of squamo us differentia
tio n (Fig. 3). T he pro mine nce of sebaceous differentiation
varied amo ng neopl asm s and in different
regions of the same neopl asm . Cystic or pigmented
basal cell neoplasm s were not seen.
Post-surgical clin ical data was ava ilable on 24 ferrets.
One of the ferrets (tumor No. 24) had clinical
ev ide nce of cardiac dysfun ction during surgery and
died soo n after surgery . A tumor (No. 15) on the tail,
which consisted primarily of baso squamo us elements,
recurred at the site. There was no repo rted recurrence
or meta stasis following amputati on of the tai l of that
ferret or in the rem ain ing ferrets .
Mastocytoma
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Nine (16%) of the cutaneo us neoplasm s were mastocytom
as. Age ofthe seven an imals where th e age was
known ranged from 3 to 6 years (mean = 4. I years,
med ian = 3 years) . Sex and site were reco rded in eight
cases. T here was no site predil ection in the four males
and four fema les.
T he cutaneo us mastocytom as in eight ferrets consisted
offocal well-circumsc ribed to slight ly infiltrative
masses in the su perficial derm is (Fig. 4). The individualized
round to ovoid mast cells typically form ed cellular
sheets, altho ugh rows of cells sometimes were
noted at the periphery of neopl asm s. The neoplastic
cells had a mod erate amo unt of cytoplasm that was
am phophilic with no discern ible granules in sections
sta ined with hem atoxylin and eosin. The centrally
placed round to ovoid nuclei had a mod erate amount
of evenly dispersed chromatin and variably prominent
nucleoli. Mitotic figures were rare. Toluidine blue
sta ini ng revealed diffuse cytoplasmic metachromasia
with a small nu m ber of distinct metachro matic cytoplasmi
c granules (Fig. 4).

502 Parker and Picut Vet Pathol 30:6. 1993
Fig. 4. Skin; tumor No. 35. Cutaneous mastocytoma consisting
of sheets of round neoplastic cells in a ferret. Note
the distinct demarcation between the tumor and the overlying
dermis. HE. Bar = 30 j.Lm . l nset: Note distinct granules
in some neoplastic cells. Toluidine blue. Bar = 8 j.Lm .
One ferre t had microscop ically di stinctive mastocyto
mas that presented as sma ll masses beh ind th e ear
and in th e flank region, wh ich were recorded as a single
case (tumor No. 33) with multicentric cutaneo us involveme
nt. Microscopi cally, both lesions consis ted of
po orly circumscribed derm al and subcuta neo us masses
co m posed of shee ts of histiocytic cells, some of which
had metach romati c cyto plasmic granules. The neoplastic
cells va ried in size and sha pe and had a sma ll
number of mitoti c figures.
The cells in six ofeight mastocytom as demonstrat ed
an affi nity for av idin-peroxidase. In positively stai ned
mast cells, the chro mage n sta ining of th e cyto plasm
was diffuse or coarsely gra nular. The intensity ofstai ning
in cells from the same neo plasm va ried from weak
to mo derate in d ifferent regions.
One ferret with mastocytoma d ied ofunknown causes,
and post-surgical clinical informa tion on ano ther
ferret was not availab le. There was no reported recurrence
or metastasis in the rema ining seve n affected
an ima ls.
Fibroma/ fibrosarcoma
Six fibromas and two fibrosarcomas were diagnosed
in eight ani ma ls. Age of the affected anima ls, which
was know n in seve n cases, ranged from 10 months to
4.5 years (mean = 2.9 years, median = 3.5 years). Five
fibromas and one fibrosarcoma were in males. Th ere
was no site pred ilect ion .
T he fibro mas were well-circumsc ribed derm al or
subcutaneo us masses that consis ted ofinterlacing bundles
of well-different iated fibroblasts surrounded by
mature collagen fibers . The fibrosarcomas were wellcircumscribed
dermal or subcutaneous masses composed
ofmoderat ely differentiated fibro blasts with collagen
fibers . The neoplastic cells in the fibrosarcom as
exhibited a mod erat e degree of cellular atypia, characterized
by prominent nucleoli and a moderat e num ­
ber of m itotic figures.
T here was no reported recurrence or metastasis of
the three fibromas or two fibrosarcom as where postsurgical
clinical informatio n was available.
Hemangioma
One hem angioma (tumor No . 5 1)consisted ofa small
black mass in the ski n of the dorsal lum bar region of
a 5-year-old fema le that also had a basal cell tumor in
the skin of the thigh (tumor No. 30). The seco nd hemangioma
(tumor No . 52) was a sma ll mass on the
pin na of a 4-year-old fema le that also had a basal cell
tu mor in the skin of the foo t (tumo r No. 42). Both
lesions consisted ofwell-circumscribed derm al masses
co mposed of blood-filled caverno us spaces lined by
well-differentiated endothelial cells.
T here was no reported recurrence or metastasis of
th e hem angiomas.
M iscellaneous neopla sms
O ne eac h of th e followi ng lesion s were diagnosed :
hem angiosarcoma, cutaneous polyp, ana l gland adenocarcin
om a, lymphosarcoma of the prepuce and inguinal
lymph nod e, and ade nocarcinoma of th e prepuce.
T he hem angiosarcom a (tumo r No . 53) was a 1- x
l- crn fluid-filled mass at the commissure ofthe lips of
a fem ale of un known age. Microscopically, the lesion
consisted of a poorl y circumscribed mass of spindleshaped
to polygona l neoplastic cells, some of which
for med sin usoi da l spaces. There was no reported recurrence
or metastasis of the hemangiosarcoma.
T he ana l gland ad enocarcin om a (tumo r No. 54) was
a 2-cm-diameter mass over th e left ana l gland of a
7-year-old neutered male. The lesio n consisted of an
infiltrative cuta neo us and subcutaneous mass composed
of neopl astic ep ithelial cells tha t for me d nests
and tubules; the tubules some times contai ning amorpho
us eos inophilic secretory ma terial. T he neopl astic
cells had vesiculated nucl ei, pro minent nucleoli, and
numerou s mitot ic figures.
T he preputial ade nocarcino ma (tumor No . 55) was
a 2- x 2-c m mass surro undi ng the prep utial ori fice of
a 6-yea r-old intact male. Microscopically, th e lesion
consisted of anaplastic epithelial cells that formed nests
and tub ules. T he neopl astic cells exhi bited seve re cellular
atypis m, with numerou s mitotic figures.
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Vet !'ath ol 30:6. 1993 Skin Tumors in Ferrets 503
The preputial gland and anal gland neoplasm s were
compatible with apocrine gland adenocarcino mas. The
preputial gland ade nocarcino ma was inoperabl e, and
the animal was eutha natized. T here was no reported
recurre nce or metastasis of the ana l gland adc nocarcmo
rna.
The preputial lym phosarco ma (tumor No . 56) was
a 2-cm -diame ter ulcerat ed mass involving the prepuce,
but not the peni s, of a 6-year-old intact male. Microscopically,
the prepuce and inguinal lymph node had
sheets ofindividualized round neoplastic cells that had
a small amount of cytoplasm , coarsely clumped chroma
tin , promi nent nu cleoli, and num erous mitoti c figures
that were co mpatible with th ose of mod erately
differentiated Iymphoblasts. Post-operat ive clin ical inform
ati on was not available.
Th e cuta neo us polyp (tumor No . 57) was a 3-mmd
iame ter mass on the right metat arsus of a 5-year-old
fem ale. Microscopica lly, the polypoid lesion consisted
ofa central zo ne offibrous connective tissue and blood
vessels covered by well-differentiated stratified squamou
s epithelium . T here was no reported recurrence or
me tas tasis.
Discussion
Cutaneous neopl asm s were co m mo n findin gs in biopsy
or necrop sy speci me ns fro m dom estic ferrets submitted
to diagnostic lab oratories and comprised 46%
of accessions in a 54-mont h period. T he mos t common
cutaneous neopl asm in th is study was basal cell tumor
33/57 (58%), followed by mastocytoma 9/57 ( 16%) and
fibro ma 6/57 (I I%). Previo us case reports 9. 11. 15.22 have
suggested that cutaneous squamous cell carci noma is
co m mo n in ferrets, no squa mo us cell carcino mas were
found in the present study. Th e grea t majorit y of the
basal cell tumors in this study included areas o f squamous
differe ntiation , but the basaloid components were
so prominent that the neop lasm s would not be c1assilled
as squamous cell carci no ma s by accepted classificatio
n criteria.
T he basal cell neoplasms were micro scopically similar
to those seen in dogs '? and to the ferre t neoplasm s
previou sly reported as basisqu amosebaceou s and sebaceou
s gland carcino mas. 19.20 T hese two term s are descriptive
of many of the lesion s seen in th e present
study , but the term " basal cell tumor " was chose n to
reflect the co m mo n origin ofthe tumors fro m basaloid
ep ithelial cells. There were no pigm ent ed or cystic basal
cell tumors, such as th ose seen in dom estic cats.v"
There was no distinct site predilection, altho ugh the
head, neck, sho ulders , legs, and feet were somewhat
more commonly involved than expected, give n the
relative surface area of ski n involved. In the overall
gro up of 142 ferrets with cuta neo us and noncutan eou s
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lesions, 58% were females, but 70% offerrets with basal
cell tumors were female.
T he ma stocytomas were microscopically benign and
were sim ilar to th ose previou sly reported in ferr ets.
T he mastocytomas were simi lar to th ose seen in domestic
cats, although the ferret lesion s lacked the follicular
lymphocytic aggregatio ns that are commonly
seen in solitary cuta neo us mastocyto mas of cats.P-"
T he sing le multicentric histiocytic mastocytoma resembled
the histiocytic variant of mastocytoma that
is most commo nly seen in Siamese cats." The ferret
mastocytomas lacked the prom inent eosinophilic infiltratio
n, ede ma , and collagen dege neratio n that are
commonly seen in canine cuta neo us mastocytomas."
Mast cell gra nules of rode nts and human beings have
an a ffi nity for av idi n th at can be dem on strat ed by sta ndard
immunohi stochemi cal sta ining procedures.v' and
avidin affinity has been reported as a method for differen
tia ting mastocytomas from other ro und cell tu ­
mors in the dog and ca1. 3 • 18 Findings in the present
stud y indicate that some ferre t mas tocytomas have
affini ty for avi din; however, avi di n stai ning had no
d iagnostic advantage over ro utine staining wit h toluidine
blue for me tachromasia.
T he fibro mas and fibrosarcomas were simi lar to those
reported in other species. The degree of cellular atypism
and mitoti c ind ex were th e basis for classificati on
oftwo masses as fibrosa rcomas, although th ose lesio ns
d id not appear to be highly aggressive.
T his study provides no conclusive information regarding
the overall prevalence ofneoplasia in the ferre t
beca use the size of the general population from whic h
these cases were derived was unknown. Cutaneous neoplasms
were commonly found among speci me ns subm
itted for ro utine histopath ologic diagnos is, but specime
ns ofthat type would be expected to contai n a large
percentage of neopl asm s. Th ese features of th e study
prohibit us from confirmi ng or refuti ng the prop osal
th at the ferre t is a low tumor incidence species.
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