injection site dog vaccine sarcoma

[malernee]

http://www.ingenta.com/isis/searching/E ... 06&index=4

Fibrosarcomas at Presumed Sites of Injection in Dogs: Characteristics
and Comparison with Non-vaccination Site Fibrosarcomas and Feline
Post-vaccinal Fibrosarcomas
Journal of Veterinary Medicine, Series A August 2003, vol. 50,
no. 6, pp. 286-291(6)
Vascellari M.[1]; Melchiotti E.[1]; Bozza M.A.[1]; Mutinelli F.[2]
[1] Address of authors: Istituto Zooprofilattico Sperimentale delle
Venezie, Histopathology Department, Viale dell'Università 10, 35020
Legnaro (PD), Italy; [2] Corresponding author:, Tel: +39 049 8084261,
Fax: +39 049 8084258, Email: fmutinelli@izsvenezie.it Abstract:
Summary
Fifteen fibrosarcomas, surgically excised from presumed sites of
injection in dogs, and 10 canine fibrosarcomas excised from sites not
used for injection were histologically and immunohistochemically
compared with 20 feline post-vaccinal fibrosarcomas. Canine
fibrosarcomas from presumed injection sites were of grade I (3), of
grade II (4) and grade III (8). Two fibrosarcomas from non-injection
sites were of grade I, four of grade II and four of grade III. Feline
samples were classified as grade I (2), grade II (4) and grade III (14).
All fibrosarcomas from presumed injection sites of both species showed
lymphocytic inflammatory infiltration located at the tumour periphery,
while two canine fibrosarcomas from non-injection sites showed
perivascular inflammatory infiltration within the neoplasm. All samples
were immunohistochemically examined for vimentin, smooth muscle actin,
muscle specific actin and desmin expression. All tumours were positive
for vimentin. Ten canine fibrosarcomas from presumed injection sites and
all feline samples contained cells consistent with a myofibroblastic
immunophenotype. Aluminium deposits were detected in eight canine
fibrosarcomas from presumed injection sites and 11 feline post-vaccinal
fibrosarcomas by the aurintricarboxylic acid method. The present study
identifies distinct similarities between canine fibrosarcomas from
presumed injection sites and feline post-vaccinal fibrosarcomas,
suggesting the possibility of the development of post-injection sarcomas
not only in cats, but also in dogs.
Document Type: Research article ISSN: 0931-184X
DOI (article):
10.1046/j.1439-0442.2003.00544.x SICI (online):
0931-184X(20030801)50:6L.286;1-

[malernee]

PATHOLOGY
Istituto Zooprofilattico Sperimentale delle Venezie, Histopathology Department, Viale dell’Universita` , Legnaro (PD), Italy
Fibrosarcomas at Presumed Sites of Injection in Dogs: Characteristics
and Comparison with Non-vaccination Site Fibrosarcomas and Feline
Post-vaccinal Fibrosarcomas
M. Vascellari, E. Melchiotti, M. A. Bozza and F. Mutinelli1
Address of authors: Istituto Zooprofilattico Sperimentale delle Venezie, Histopathology Department, Viale dell’Universita` 10,
35020 Legnaro (PD), Italy; 1Corresponding author: Tel.: +39 049 8084261; fax: +39 049 8084258;
E-mail: fmutinelli@izsvenezie.it
With 3 figures and 3 tables Received for publication: September 13, 2002
Summary
Fifteen fibrosarcomas, surgically excised from presumed sites
of injection in dogs, and 10 canine fibrosarcomas excised from
sites not used for injection were histologically and immunohistochemically
compared with 20 feline post-vaccinal fibrosarcomas.
Canine fibrosarcomas from presumed injection sites
were of grade I (3), of grade II (4) and grade III (8). Two
fibrosarcomas from non-injection sites were of grade I, four of
grade II and four of grade III. Feline samples were classified as
grade I (2), grade II (4) and grade III (14). All fibrosarcomas
from presumed injection sites of both species showed lymphocytic
inflammatory infiltration located at the tumour periphery,
while two canine fibrosarcomas from non-injection sites
showed perivascular inflammatory infiltration within the neoplasm.
All samples were immunohistochemically examined for
vimentin, smooth muscle actin, muscle specific actin and desmin
expression. All tumours were positive for vimentin. Ten
canine fibrosarcomas from presumed injection sites and all
feline samples contained cells consistent with a myofibroblastic
immunophenotype. Aluminium deposits were detected in eight
canine fibrosarcomas from presumed injection sites and 11
feline post-vaccinal fibrosarcomas by the aurintricarboxylic
acid method. The present study identifies distinct similarities
between canine fibrosarcomas from presumed injection sites
and feline post-vaccinal fibrosarcomas, suggesting the possibility
of the development of post-injection sarcomas not only
in cats, but also in dogs.
Introduction
Dogs and cats can sometimes develop subcutaneous inflammatory
reactions at sites of injection, and there is some
evidence to further suggest that, although other drugs may be
involved, those reactions are mainly associated with the use of
inactivated virus vaccines containing aluminium-based adjuvants
(Hendrick, 1998). In both dogs and cats, the development
of necrotizing panniculitis at sites of rabies vaccine
administration was first observed by Hendrick and Dunagan
(1991). These lesions were characterized by a central area of
necrosis rimmed by an inflammatory reaction, often with
lymphatic follicles formation. Moreover, in cats a distinctive
tumour which developed at sites of rabies and feline leukaemia
vaccine administration, was noted by Hendrick and Goldschmidt
(1991). Feline post-vaccinal fibrosarcomas (Hendrick
et al., 1998) have received a great deal of attention in
veterinary literature over the past 10 years. These neoplastic
lesions seem to arise in younger cats and seem to be more
aggressive, with a higher recurrent rate, than fibrosarcomas
arising at other sites (Hendrick, 1998). Histologically, feline
post-vaccinal fibrosarcomas are characterized by inflammatory
peritumoural infiltration, multinucleated giant cells and myo-
fibroblastic cells (Dubielzig et al., 1993). Grey–brown granular
to crystalline foreign material was found within macrophages
in the inflammatory foci in 42 of 198 post-vaccinal sarcomas,
and in three cases the electron probe X-ray analysis demonstrated
that it was composed of aluminium and oxygen
(Hendrick et al., 1992). Post-vaccinal fibrosarcomas are
believed to arise as a result of proliferation of fibroblasts and
myofibroblasts at sites of chronic inflammation induced by the
vaccine’s adjuvants, its antigens, or both (Macy and Hendrick,
1996).
Fibrosarcoma is the second most prevalent skin tumour in
cats, while in dogs it represents a rare tumour (Yager and
Wilcock, 1994).
In the present study, 15 cases of canine fibrosarcomas
arising at presumed sites of injections and 10 canine fibrosarcomas
developing at sites not used for injections (oral cavity,
legs) were examined and histologically and immunohistochemically
compared with 20 feline post-vaccinal fibrosarcomas.
Materials and Methods
Animals and tissue processing
Paraffin blocks containing fibrosarcomas surgically excised
from dogs and cats between 1998 and 2001 were retrieved from
the archives of the Histopathology Department of the Istituto
Zooprofilattico Sperimentale delle Venezie (northern Italy).
Fifteen canine fibrosarcomas, arising at sites commonly used
U.S. Copyright Clearance Center Code Statement: 0931–184X/2003/5006–0286 $15.00/0 www.blackwell.de/synergy
J. Vet. Med. A 50, 286–291 (2003)

2003 Blackwell Verlag, Berlin
ISSN 0931–184X
by veterinarians for subcutaneous injections (back of the neck,
inter-scapular region, thorax) comprised the group of
fibrosarcomas
from presumed injection sites. All dogs had been
vaccinated regularly against the most common canine infectious
diseases (infectious gastroenteritis, distemper, infectious
hepatitis and leptospirosis), and six dogs received also rabies
vaccines. Ten canine fibrosarcomas from sites not used for
injections and 20 feline post-vaccinal fibrosarcomas, showing
typical histopathological characteristics (Hendrick et al.,
1998), were examined for comparison. The cats included in
the present study had been vaccinated regularly against feline
leukaemia virus (FeLV) and other common feline infectious
diseases.
For each specimen, 4-lm-thick sections were stained with
haematoxylin and eosin and examined microscopically in
order to grade the neoplasia and to investigate the presence
of an inflammatory reaction. The grading scheme, previously
adapted to the dog (Powers et al., 1995) and recently applied
to feline post-vaccinal fibrosarcomas (Couto et al., 2002),
was based on cellular differentiation, presence and extension
of necrosis within the neoplasm and mitotic rate. All
fibrosarcomas were scored 1–3 for overall differentiation
(1 ¼ tumours closely resembling the mature differentiation;
2 ¼ tumours that had a defined histological phenotype;
3 ¼ poorly differentiated tumours), mitotic rates (1 ¼ 1–9
mitotic figures per ten 400· fields; 2 ¼ 10–19 mitotic figures
per ten 400· fields; 3 ¼ 20 or more mitotic figures per ten
400· fields) and necrosis (1 ¼ no necrosis; 2 ¼ <50% of the
total area; 3 ¼ >50% of the total area). Final scores of three
or four were designated grade I; scores of five or six were
designated grade II; scores of seven, eight or nine were
designated grade III.
A computer program was used for the statistical analysis
(stata). Comparison between canine tumour categories with
respect to the grade was performed using the Kruskal–Wallis
non-parametric analysis of variance (anova). A level of
significance of 0.05 (P < 0.05) was used.
Immunohistochemistry
For each sample, 3 lm sections were cut and immunohistochemically
stained for vimentin (V9, DAKO, Carpinteria, CA,
USA, M0725, 1 : 25), desmin (DE-R-11, DAKO, Carpinteria,
CA, USA, M724, 1 : 50), smooth muscle actin (1A4, DAKO,
Carpinteria, CA, USA, M851, 1 : 50), and muscle specific
actin (MSA) (HHF35, DAKO, Carpinteria, CA, USA,
M0635, 1 : 50) (Inter-Species Cross-Reactivity of DAKO
antibodies, Code N 10 145). Each primary antibody was
incubated for 30 min at room temperature. Antigen retrieval
for desmin and smooth muscle actin was obtained by
trypsinization for 30 min at 37C. The EnVisionTM Detection
Kit Peroxidase/DAB Rabbit Mouse (DAKO, Carpinteria, CA,
USA, K5007) was applied. The sections were counterstained
with Mayer’s haematoxylin.
Histochemistry
For the detection of aluminium deposits in tissues, the
aurintricarboxylic acid method was applied to the sections.
Aluminium deposits appeared red under light microscopy
(Bonucci, 1981).
Results
Canine fibrosarcomas from presumed injection sites
The average age of dogs with fibrosarcomas at presumed
injection sites was 6.2 years (7 months–11 years) (Table 1).
Samples were characterized by a subcutaneous proliferation
of neoplastic cells, of a mesenchymal phenotype and a variable
degree of pleomorphism and mitotic rate. Neoplasms were
sometimes pseudo-encapsulated and showed infiltrative
growth. According to the grading scheme introduced, on the
basis of cellular differentiation, mitotic rate and extension of
necrosis, samples were classified as grade I (3), grade II (4) and
grade III (8). All samples exhibited an inflammatory infiltration,
mainly composed of lymphocytes, macrophages and
plasma cells, localized at the tumour periphery, often in a
follicle-like arrangement (Fig. 1).
Immunohistochemically, all fibrosarcomas were strongly
positive for vimentin, and negative for desmin. Eight samples
showed bundles of cells, mainly located at the tumour
periphery, which stained positive for smooth muscle actin
and 10 samples contained bundles of cells, which stained
Table 1. Case summaries for 15 dogs with fibrosarcomas from presumed injection sites
Case Breed Age (years) Sex Location Vaccine history Aluminium
1 Collie 5 M Shoulder Regularly vaccinated +
2 Mixed 11 M Shoulder Rabies +
3 Mixed 10 F Thorax Regularly vaccinated )
4 Mixed 10 M Thorax Regularly vaccinated +
5 German Shepherd dog 8 F Thorax Rabies )
6 Mixed 2 M Back Regularly vaccinated )
7 Schnauzer 3 M Shoulder Rabies )
8 Chow-Chow 8 M Shoulder Regularly vaccinated )
9 Golden Retriever 2 M Shoulder Regularly vaccinated +
10 American pit bull 1 F Shoulder Regularly vaccinated )
11 Mixed 6 M Back Rabies +
12 Mixed 10 M Thorax Regularly vaccinated )
13 Siberian Husky 11 M Shoulder Rabies +
14 Drahthaar 7 months F Back Regularly vaccinated +
15 Irish setter 5 M Shoulder Rabies +
M, male; F, female; regularly vaccinated ¼ vaccinated against the common canine infectious diseases; rabies, vaccinated against the common
canine infectious diseases and rabies.
Fibrosarcomas at Presumed Sites of Injection in Dogs 287
positive for MSA (Fig. 2). These cells showed a fibroblastic
phenotype, with abundant cytoplasm and elongated nuclei.
Aluminium deposits were detected in eight fibrosarcomas,
both within macrophages and in the fibrous stroma (Table 1;
Fig. 3).
Canine fibrosarcomas from sites not used for injection
The average age of dogs with fibrosarcomas from sites not
used for injection was 8.4 years (5–11 years) (Table 2).
Two samples were of grade I, four of grade II and four of
grade III. Neoplasms were not encapsulated and locally
infiltrative. Two fibrosarcomas, from gum and foreleg, showed
ulceration of the mucous membrane and cutis, respectively,
and perivascular inflammatory infiltration within the neoplastic
mass.
When tested by immunohistochemistry, all samples were
strongly positive for vimentin and negative for desmin. Single
cells positively stained for MSA antigen were detected within
two fibrosarcomas. Aluminium deposits were not detected in
any sample.
Feline post-vaccinal fibrosarcomas
The average age of cats included in the present survey was
8.4 years (5–13 years) (Table 3). Samples included two fibrosarcomas
of grade I, four of grade II and 14 of grade III. All
samples showed lymphocytic aggregates at the periphery of the
neoplastic proliferation. Multinucleated giant cells were detected
in 10 fibrosarcomas.
Immunohistochemically, all samples were strongly positive
for vimentin. Bundles of neoplastic cells positive stained for
the smooth muscle actin were detected at the periphery of 16
feline fibrosarcomas. Eighteen samples showed cells positive
stained for MSA. Only one feline post-vaccinal fibrosarcoma
showed few single cells positive for desmin. Aluminium
deposits were detected in 11 fibrosarcomas by the aurintricarboxylic
acid method.
Fig. 1. Canine fibrosarcoma from presumed injection site. The
inflammatory reaction (arrow) composed of lymphocytes and rare
plasma cells was located at the tumour periphery. HE. Bar ¼ 50 lm.
Fig. 2. Canine fibrosarcoma from presumed injection site. Muscle
specific actin antigen is expressed by cells located in the tumour
periphery. EnVisionTM Detection Kit Peroxidase with HHF35
antibody and haematoxylin counterstain. Bar ¼ 50 lm.
Fig. 3. Canine fibrosarcoma from presumed injection site. Aluminium
deposits revealed by the aurintricarboxylic acid method in the fibrous
stroma of the excised tumours. Bar ¼ 25 lm.
Table 2. Case summaries for dogs with fibrosarcomas from sites not
used for injection
Case Breed Age (years) Sex Location
1 Mixed 7 F Gum
2 German shepherd dog 11 F Foreleg
3 Doberman 10 F Gum
4 Mixed 11 M Gum
5 Rottweiler 6 M Gum
6 Dalmatian 5 F Hind leg
7 Mixed 7 F Lip
8 German shepherd dog 6 F Gum
9 German shepherd dog 11 M Gum
10 Bloodhound 10 M Foreleg
M, male; F, female.
288 M. Vascellari et al.
Discussion
Fibrosarcoma is a rare tumour in dogs, and its most common
sites of development are the skin of the trunk and of the
proximal limbs as well as the oral cavity (Yager and Wilcock,
1994).
Canine fibrosarcomas arising at presumed sites of subcutaneous
injection (shoulder, inter-scapular region, thorax) were
examined and morphologically and immunohistochemically
compared with canine fibrosarcomas arising at sites not used
for injection and feline post-vaccinal fibrosarcomas.
The average age of dogs with fibrosarcomas from presumed
injection sites was 6.2 years. The average age of dogs with
fibrosarcomas at sites not used for injection was 8.5 years
while that of cats was 8.4 years. According to the literature,
the average age of cats with fibrosarcomas at sites not used for
injection is 12 years (Gross et al., 1992), while post-vaccinal
fibrosarcomas are reported to arise in cats with an average age
of 8.1 years (Hendrick et al., 1994) and 8.6 years (Doddy
et al., 1996), respectively. The average age of dogs with
fibrosarcomas, irrespective of the site of development, was
reported as 10 years (Gross et al., 1992). The comparison
between the average age of the three classes of animals was
statistically analysed and no significant difference was detected.
Although epidemiological evaluations are not possible due
to the limited number of cases included in the present study,
the young age of some dogs with presumed post-injection
fibrosarcomas supports the hypothesis of an iatrogenic origin.
The three groups of neoplasms were histologically examined
for morphological distinctions. The grading scheme applied,
was the one used in categorizing canine soft-tissue sarcomas
(Powers et al., 1995) and feline post-vaccinal fibrosarcomas
(Couto et al., 2002) and allowed the separation of the
neoplasms into three classes with increasing malignancy.
Histological grading is the most important prognostic factor
for human adult soft-tissue sarcomas with regard to the
probability of metastasis development and survival rate
(Kandel et al., 1999; Mandard et al., 1989). It has been shown
that feline post-vaccinal fibrosarcomas exhibit histopathological
features consistent with a more aggressive biologic
behaviour than fibrosarcomas at sites not used for injection
(Doddy et al., 1996). The statistical analysis applied to the
tumour grades in this study did not reveal significant differences
between the two different groups of canine fibrosarcomas.
In both species the fibrosarcomas surgically excised from
presumed sites of injection showed an inflammatory response,
mainly as lymphatic follicle-like aggregates located at the
tumour periphery. In contrast, only two canine fibrosarcomas,
excised from the gum and the foreleg, were accompanied by
perivascular infiltration of lymphocytes within the neoplasm.
In these cases, the inflammatory reaction was probably the
consequence of ulceration of the mucous membrane and cutis
lining the fibrosarcomas, respectively. The inflammatory
response is one of the distinctive features of the feline postvaccinal
fibrosarcomas (Doddy et al., 1996). Data suggest that
local inflammation caused by aluminium or other potentially
irritant inoculated substances, may predispose tissues to
tumour development. Furthermore, feline fibrosarcomas
found in vaccine sites are histologically identical to those
observed in previously traumatized areas (Smith, 1995).
However, the role of lymphocytes in tumourigenesis or host
response to neoplasia is still unknown (Couto et al., 2002).
Multinucleated giant cells were detected in 10 feline postvaccinal
fibrosarcomas, whereas they were not detected in any
canine sample. The presence of multinucleated giant cells is a
common finding in feline fibrosarcomas and is regarded as an
indicator of a less differentiated phenotype (Doddy et al.,
1996). In human oncology, the presence of multinucleated
giant cells is correlated with an aggressive, invasive tumour
phenotype and is used as part of a paradigm to estimate
prognosis (Couto et al., 2002).
Tumours were tested immunohistochemically for vimentin,
actin and desmin expression. All samples were strongly
positive for vimentin, thus confirming the mesenchymal origin
of the neoplastic cells.
Myofibroblasts are interesting cells identified for the first
time in contractile granulation tissue and wounds in the early
1970s (Mentzel and Fletcher, 1997). Ultrastructurally, myofi-
broblasts are recognized by their features of both fibroblasts
and smooth muscle actin. Immunohistochemistry identified
four mainly myofibroblastic phenotypes which show, in
addition to cytoplasmic b- and c-actins, immunopositivity
for vimentin, vimentin and desmin, vimentin and alphasmooth
muscle actin, or vimentin, alpha-smooth muscle actin,
and desmin (Mentzel and Fletcher, 1997). In the present study,
immunolabelling of tumours with muscular antigens allowed
the identification of bundles of cells with a myofibroblast-like
immunophenotype in all the feline and in 10 canine fibrosarcomas
from presumed injection sites. These cells were localized
at the tumour periphery, often adjacent to lymphatic folliclelike
aggregates. It is generally accepted that myofibroblasts
represent an important component of numerous benign and
malignant mesenchymal neoplasms. In addition to tissue
repair process and stromal response to neoplasia, proliferating
myofibroblasts are the main cellular component in four
pathological settings: reactive lesions, benign tumours, locally
aggressive fibromatoses and sarcomas with myofibroblastic
differentiation (Mentzel and Fletcher, 1997). Myofibroblasts
were previously detected in feline post-vaccinal fibrosarcomas,
identified by both immunohistochemistry and electron
microscopy (Dubielzig et al., 1993; Madewell et al., 2001).
Table 3. Case summaries for cats with post-vaccinal fibrosarcomas
Case Breed Age (years) Sex Location
1 DSH 10 M Shoulder
2 DSH 7 F Shoulder
3 DSH ns M Shoulder
4 Persian 9 F Neck
5 DSH 7 F Shoulder
6 DSH 13 M Shoulder
7 DSH 9 F Shoulder
8 Persian 10 F Shoulder
9 DSH 8 F Shoulder
10 DSH 6 M Shoulder
11 DSH 7 F Shoulder
12 Persian 7 M Back
13 DSH 9 F Back
14 DSH 8 M Shoulder
15 DSH 5 F Lateral thorax
16 DSH 8 M Back
17 DSH 7 M Neck
18 DSH 13 M Shoulder
19 DSH 10 F Back
20 DSH 6 M Lateral thorax
DSH, domestic short haired; ns, non-specified; M, male; F, female.
Fibrosarcomas at Presumed Sites of Injection in Dogs 289
The function and biological implications of myofibroblasts in
tumour growth are far from being clarified. One recent study
performed on a rat colorectal tumour model (Lieubeau et al.,
1999), suggests that myofibroblasts, due to their contractive
properties, are able to form a capsule that enveloped neoplastic
nodules, mechanically preventing penetration of T lymphocytes
and macrophages into the tumour, while promoting
tumour growth and progression. In fact, locomotion and
tumour access of immune cells is crucial for the function of the
immune system. If this mechanical action should be the same
in injection-associated fibrosarcomas, it may account for the
presence of abundant lymphocytes along the periphery of the
tumours and for their more aggressive biological behaviour
than fibrosarcomas at sites not used for injections. In canine
fibrosarcomas from non-injection sites, there was no evidence
of myofibroblastic differentiation. The single cells positive for
MSA, which were observed in two cases, are considered
consistent with normal muscular cells entrapped in the
neoplastic proliferation.
Aluminium deposits were detected in eight canine fibrosarcomas
from presumed injection sites and 11 feline fibrosarcomas
by histochemistry. The aurintricarboxylic acid
method is a specific method for the identification of aluminium
hydroxide deposits in tissues (Bonucci, 1981). Aluminium
hydroxide adjuvants are used in many veterinary and human
inactivated vaccines. In animals it has been detected at sites
of subcutaneous injection for up to 1 year after application
(Madewell et al., 2001). Aluminium deposits were previously
highlighted in three of 198 feline post-vaccinal fibrosarcomas
by electron probe X-ray analysis and ultrastructurally
(Hendrick et al., 1992; Madewell et al., 2001), suggesting
the role of aluminium-containing adjuvant as irritant in the
pathogenesis of these fibrosarcomas. The development of
foreign body granulomas caused by aluminium has also been
reported in humans (Hendrick et al., 1992; Fawcett and
Smith, 1984). All the animals included in the present study
received annual vaccinations and underwent surgery soon
after the first observation of the neoplastic growth by the
owners or veterinarians. Such a special care paid to these
pets, assuring a prompt recognition and removal of the
nodules, may have guaranteed short intervals between onset
of neoplastic growth and histochemical examination, thus
resulting in a high percentage of samples containing aluminium
deposits. Furthermore, four of eight samples containing
aluminium deposits were excised from dogs that had received
vaccination against rabies, other than against the most
common infectious diseases. The development of necrotizing
panniculitis after rabies vaccine administration has already
been reported in dogs (Hendrick and Dunagan, 1991). Rabies
vaccines have also been associated with the development of
fibrosarcomas in cats (Hendrick and Goldschmidt, 1991).
Furthermore, it is accepted that substances other than
aluminium can be involved in the pathogenesis of these
fibrosarcomas. For close to 100 years, investigators have
observed that irritation, inflammation and/or wounds are
promoters of tumour development (Macy and Hendrick,
1996). Virtually anything that causes a local inflammatory
reaction may potentially be responsible for neoplastic initiation
(Withrow and MacEwen, 2001). Sarcomas developing
at sites of subcutaneous administration of long acting drugs
and at sites with deep non-absorbable sutures, as well as
ocular post-traumatic sarcomas, are clinical examples that
support these findings (Dubielzig, 1984; Dubielzig et al.,
1990; Esplin et al., 1999; Buracco et al., 2002).
Although the post-vaccinal fibrosarcoma has been considered
as a specific entity in the cat, many similar features were
noted in feline and canine samples. In both species, fibrosarcomas
arose at the same sites, probably used by practitioners
for subcutaneous injections. The lesions were characterized by
the proliferation of mesenchymal neoplastic cells, consistent
with fibroblasts, with areas of necrosis and peritumoural
inflammatory infiltration. Cells with a myofibroblastic phenotype
were detected immunohistochemically in fibrosarcomas
from presumed injection sites of both species, but not in the
canine fibrosarcomas arising at sites not used for injection.
Aluminium deposits were noted not only in feline samples, but
also in eight canine fibrosarcomas, from presumed injection
sites.
In conclusion, the findings of this study support the
hypothesis that post-injection fibrosarcomas do not only occur
in cats but also in dogs. However, further investigations are
needed to elucidate the possible relationship between vaccine
administration and fibrosarcoma development at sites of
injection in dogs.
Acknowledgements
We wish to thank the veterinary practitioners who submitted
the canine and feline samples included in the present study.
References
Bonucci, E., 1981: Manuale di istochimica. Lombardo Editore, Roma.
Buracco, E., M. Martano, E. Morello, and A. Ratto, 2002: Vaccine
associated-like fibrosarcoma in the site of a deep nonabsorbable
suture in a cat. Vet. J. 163, 105–107.
Couto, S. S., S. M. Griffey, P. C. Duarte, and B. R. Madewell, 2002:
Feline vaccine-associated fibrosarcoma: morphologic distinctions.
Vet. Pathol. 39, 33–41.
Doddy, F. D., L. T. Glickman, N. W. Glickman, and E. B. Janovits,
1996: Feline fibrosarcomas at vaccination sites and non-vaccination
sites. J. Comp. Pathol. 114, 165–174.
Dubielzig, R. R., K. L. Hawkins, and P. E. Miller, 1993: Myofibroblastic
sarcoma originating at the site of rabies vaccination in a cat.
J. Vet. Diagn. Invest. 5, 637–638.
Dubielzig, R. R., 1984: Ocular sarcoma following trauma in three cats.
J. Am. Vet. Med. Assoc. 184, 578–581.
Dubielzig, R. R., J. A. Everitt, J. A. Shadduck, and D. M. Albert,
1990: Clinical and morphologic features of post-traumatic ocular
sarcomas in cats. Vet. Pathol. 27, 62–65.
Esplin, D. G., M. Bigelow, L. D. McGill, and S. R. Wilson, 1999:
Fibrosarcoma at the site of a Lufenuron injection in a cat. Vet.
Cancer Soc. Newsletter 23, 8–9.
Fawcett, H. A., and N. P. Smith, 1984: Injection-site granuloma due to
aluminium. Arch. Dermatol. 120, 1318–1322.
Gross, T. L., P. J. Ihrke, and E. J. Walder, 1992: Veterinary Dermatopathology.
Mosby Year Book, St. Louis.
Hendrick, M. J., and M. H. Goldschmidt, 1991: Do injection site reactions
induce fibrosarcoma in cats? J. Am. Vet. Med. Assoc. 99, 968.
Hendrick, M. J., and C. A. Dunagan, 1991: Focal necrotizing granulomatous
panniculitis associated with subcutaneous injection of
rabies vaccine in cats and dogs: 10 cases (1988–1989). J. Am. Vet.
Med. Assoc. 198, 304–305.
Hendrick, M. J., M. H. Goldschmidt, F. S. Shofer, Y. Y. Wang, and
A. P. Somlyo, 1992: Postvaccinal sarcomas in the cat: epidemiology
and electron probe microanalytical identification of aluminium.
Cancer Res. 52, 5391–5394.
290 M. Vascellari et al.
Hendrick, M. J., 1998: Historical review and current knowledge of risk
factors involved in feline vaccine-associated sarcomas. J. Am. Vet.
Med. Assoc. 213, 1422–1423.
Hendrick, M. J., F. S. Shofer, M. H. Goldschmidt, J. C. Haviland,
S. H. Schelling, S. J. Engler, and J. M. Gliatto, 1994: Comparison of
fibrosarcomas that developed at vaccination sites and at nonvaccination
sites in cats: 239 cases (1991–1992). J. Am. Vet. Med. Assoc.
205, 1425–1429.
Hendrick, M. J., E. A. Mahaffey, F. M. Moore, J. H. Vos, and
E. J. Walder, 1998: Histological classification of mesenchymal
tumors of skin and soft tissues of domestic animals. WHO, Second
series, Vol. II, AFIP, Washington, D.C.
Kandel, R. A., R. S. Bell, J. S. Wunder, B. O’Sullivan, C. N. Catton,
L. M. White, and A. M. Davis, 1999: Comparison between a 2- and
3-grade system in predicting metastatic-free survival in extremity
soft tissue sarcoma. J. Surg. Onc. 79, 77–82.
Lieubeau, B.,M. F.Heymann, F.Henry, I. Barbieux, K. Meflah, and M.
Gregoire, 1999: Immunomodulatory effects of tumor-associated
fibroblasts in colorectal tumor development. Int. J.Cancer 81, 629–636.
Macy, D. W., and M. J. Hendrick, 1996: The potential role of
inflammation in the development of postvaccinal sarcomas in cats.
Vet. Clin. North Am. Small Anim. Pract. 26, 103–109.
Madewell, B. R., S. M. Griffey, M. C. McEntee, V. J. Leppert, and
R. J. Munn, 2001: Feline vaccine associated fibrosarcoma: an
ultrastructural study of 20 tumors (1996–1999). Vet. Pathol. 38,
196–202.
Mandard, A. M., J. F. Petiot, J. Marnay, J. C. Mandard, J. Chasle,
E. de Ranieri, P. Dupin, P. Herlin, J. de Ranieri, A. Tanguy, N.
Boulier, and J. S. Abbattucci, 1989: Prognostic factors in soft tissue
sarcomas. A multivariate analysis of 109 cases. Cancer 63, 1437–
1451.
Mentzel, T., and C. D. M. Fletcher, 1997: The emerging role of
myofibroblasts in soft tissue neoplasia. Am. J. Clin. Pathol. 107,
2–4.
Powers, B. E., P. J. Hoppes, and E. J. Ehrhart, 1995: Tumor diagnosis,
grading and staging. Semin. Vet. Med. Surg. (Small Anim.) 10,
158–157.
Smith, C. A., 1995: Are we vaccinating too much. J. Am. Vet. Med.
Assoc. 207, 421–425.
Withrow, S. J., and E. G. MacEwen, 2001: Small animal clinical
oncology. W.B. Saunders Company, Philadelphia.
Yager, J. A., and B. P. Wilcock, 1994: Color atlas and text of surgical
pathology of the dog and cat. Mosby Year Book Europe Limited,
London.
Fibrosarcomas at Presumed Sites of Injection in Dogs 291