Veterinary Dermatology 2003, 14, 333337

Feline plasma cell pododermatitis: a study of 8 cases

Blackwell Publishing Ltd.

PATRCIA DIAS PEREIRA and AUGUSTO M. R. FAUSTINO

ICBAS Instituto de Cincias Biomdicas de Abel Salazar, Universidade do Porto, Largo Prof Abel Salazar,
Porto 4099-003, Portugal

(Received 7 December 2002; accepted 20 June 2003)

Abstract Eight cases of feline plasma cell pododermatitis, collected over a 3-year period, were studied using
histological (haematoxylin and eosin), histochemical (methyl greenpyronin) and immunohistochemical
(antibody against lambda light chains of immunoglobulins) techniques. No sex, breed or age predisposition,
or paw predilection was observed. The disease began as a swelling of the footpads, followed by ulceration.
Histologically, lesions were characterized by the presence of a large number of plasma cells in a predominantly
perivascular pattern. Binucleated plasma cells and mitotic figures were observed. Clinical follow-up for over
1 year revealed total remission of the lesions both after glucocorticoid therapy in four cases, and total surgical
excision in two animals. Follow-up studies were not possible in one case.

Keywords: feline, footpads, plasma cell, pododermatitis.

INTRODUCTION MATERIALS AND METHODS

Feline plasma cell pododermatitis is a rare skin disease
of cat footpads. The aetiopathogenesis is unknown, but
persistent hypergammaglobulinemia, marked plasma
cell tissue infiltrate and the beneficial response to gluco-
corticoid therapy strongly suggest an immune-mediated
basis for the disease.14
Clinically, feline plasma cell pododermatitis begins
as a soft, nonpainful spongy swelling of multiple foot-
pads, which in some cases become ulcerated causing
haemorrhage and lameness.1,3 In some cats concurrent
plasmacytic stomatitis,5 renal amyloidosis or immune-
mediated glomerulonephritis is reported.6
Histologically, the lesion consists of an intense inflam-
matory infiltrate composed of mature plasma cells with
prominent Russell bodies, in a predominantly perivas-
cular pattern.1,4,7 In ulcerated lesions a large number
of neutrophils and macrophages may be present and
vasculitis is occasionally seen.5
In some cases, spontaneous remission of the lesions
occurs, whereas in others there is a seasonal exacerba-
tion of the disease. Feline plasma cell pododermatitis
responds well to both glucocorticoid therapy and to wide
surgical excision of affected footpads.3,811
Here we present a clinical, histopathological and
immunohistochemical study of eight cases of feline
plasma cell pododermatitis.
Correspondence: Augusto M. R. Faustino, ICBAS Instituto de
Cincias Biomdicas de Abel Salazar, Universidade do Porto,
Largo Prof Abel Salazar, Porto 4099-003, Portugal. E-mail:
a_faustino@yahoo.com
Biopsies from eight cases of feline plasma cell podo-
dermatitis were collected between 1999 and 2001 at
the Laboratory of Veterinary Pathology of Instituto
de Cincias Biomdicas de Abel Salazar, University of
Porto. Samples were fixed in 10% formalin, dehydrated,
embedded in paraffin wax and three consecutive sections
were cut from each block.
One section was stained with haematoxylin & eosin
(H&E) and the second with methyl greenpyronin, a
stain that allows differentiation between DNA and
RNA. The methyl green dye binds to DNA, giving it a
bluegreen colour, whereas RNA is coloured red with
pyronin.12 The third section was used for immunohis-
tochemistry, performed according to the modified
avidinbiotinperoxidase complex (ABC) method.13
Briefly, sections were dewaxed, rehydrated and then
submitted to proteolytic digestion by immersion in 10%
target retrieval solution (Dako, Denmark) and incubated
in a water bath at 100 C for 20 min. Endogenous
peroxidase activity was blocked by treatment with 0.3%
hydrogen peroxide (Merck, Germany) in methanol
(Merck) for 10 min. Sections were then incubated in a
moist chamber for 20 min with normal rabbit serum
(Dako) diluted 1:5 in bovine serum albumin (BSA;
Sigma, USA), to eliminate nonspecific staining. Excess
serum was removed and the sections were incubated
overnight at 4 C, with a polyclonal antibody against
lambda light chains of immunoglobulins (clone H0070,
Dako), diluted 1:2. Subsequently, slides were incubated
for 30 min with a 1:200 dilution of biotin-labelled
antirabbit secondary antibody (Dako) and then with
the avidinbiotinperoxidase complex (Dako), for a
further 30 min. The colour was developed by incubation

2003 European Society of Veterinary Dermatology 333

334 P. D. Pereira and A. M. R. Faustino

with diaminobenzidine (Dako) for 7 min. After coun-

terstaining tissue sections with haematoxylin, slides
were mounted in Entellan (Merck). A positive reaction
was indicated by the presence of brown cytoplasmic
staining and a human plasma cell epulis was used as
the positive control.
Clinical follow-up was performed for a minimum of
one year by direct contact with clinicians and/or owners.

RESULTS

In this study no sex, breed or age predilection was

observed (Table 1). The disease affected male (n = 5) as
Figure 1. Case number 8. Ulcerated left central metacarpal footpad.
well as female (n = 3) cats. Six animals were Domestic
Short Hairs and two were Siamese. Although in two
cases the animals ages were not known, all the others
were young adults, with ages ranging from 3 to 7 years
(mean 4.7 years). The lesions affected both hindlimbs
and forelimbs, as well as right and left feet. There was no
evidence of a seasonal predisposition at the beginning
of the disease. Only two animals, one male and one
female (cases 6 and 8), were neutered. One cat was FIV
positive and the remaining seven were not checked for
FIV infection (Table 1).
The lesions began as an asymptomatic, soft, spongy
swelling of single or multiple footpads (Table 1), some
of which regressed spontaneously but recurred period-
ically. Only when the lesion became ulcerated, having a
bed of friable red granulation tissue (Fig. 1), and causing
Figure 2. Inflammatory infiltrate in a predominantly perivascular
pain and lameness, were cats presented for consultation.
pattern. H&E (400).
Biopsy was performed in six cases and wide surgical
excision was carried out in the other two.
Histological examination revealed no major differ- nucleus was bluish (Fig. 3). Plasma cells were also
ences between the eight cases. Footpad structure was identified immunohistochemically by the presence of
severely distorted due to the presence of an abundant multiple brown cytoplasmic granules (Fig. 4), con-
inflammatory infiltrate extending from the dermis to firming the production of immunoglobulin light chain
the underlying adipose tissue, in a predominantly perivas- by these cells. Binucleated plasma cells (Fig. 5) and mitotic
cular pattern (Fig. 2). The infiltrate was composed almost figures (Fig. 6) were also seen. The lesions were highly
entirely of mature plasma cells in which a juxtanuclear vascularized, with prominent congested vessels and,
pale area, representing the Golgi apparatus, was observed. in some of them, leukocytosis was observed. Leukocyto-
The identity of plasma cells was confirmed histochem- clastic vasculitis was observed in four cases. In another
ically using the methyl greenpyronin technique. With case vascular medial hypertrophy was present. All lesions
this method, the cytoplasm stained red, because of its were extensively ulcerated with numerous neutrophils
abundant rough endoplasmic reticulum, while the and mast cells present.

Table 1. Clinical details of the cats with plasma cell pododermatitis included in this study
Age Follow-up
Case Sex Breed ( years) Location FIV status Treatment period
1 Entire female DSH 4 Metacarpal R Unknown Not available
Metatarsal R + L Not checked
2 Entire male Siamese 3 Metacarpal R + L Not checked Surgical excision 1 year
3 Entire male DSH Unknown Metacarpal R Positive Prednisolone 1 mg kg1 day PO 4 years
4 Entire male DSH 7 Metacarpal L Not checked Prednisolone 1 mg kg1 day PO 2.5 year
5 Entire male DSH Unknown Metacarpal L Prednisolone 2 mg kg1 day PO 1 year
Metatarsal R Not checked
6 Neutered male DSH 5 Metacarpal R Not checked Surgical excision 1 year
7 Entire female DSH 6 Metatarsal R Not checked Prednisolone 2 mg kg1 day PO 1 year
8 Neutered female Siamese 3 Metacarpal L Not checked Prednisolone 4.4 mg kg 1 day PO 1 year
DSH, Domestic Short Hair; R, right paw; L, left paw; PO, orally.

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 Feline plasma cell pododermatitis
Figure 3. Plasma cells stained with methyl greenpyronin method,
which stains the cytoplasm red and the nucleus blue. Methyl green
pyronin (400).
Figure 4. Plasma cells immunostained with antibody against lambda
light chains of immunoglobulins. Avidinbiotinperoxidase method,
clone H0070 (400).
Figure 5. Binucleated plasma cell (arrow). H&E (1000).
Of the eight animals in this study, five were treated
with glucocorticoids (14.4 mg kg1 prednisolone orally
per day) for a period ranging from 1 to 2 months, result-
ing in total remission of the lesions (Table 1). In two
other cases, wide surgical excision of the affected
footpads, accompanied by antibacterial therapy, also
resulted in complete resolution of the lesions. With both
treatment modalities no relapse occurred in follow-up
2003 European Society of Veterinary Dermatology, Veterinary Dermatology, 14, 333337
335
Figure 6. Mitotic figure. H&E (1000).
periods of over 1 year. Follow-up was not possible in one
case. One cat (case 3) died 4 years after the diagnosis of
feline plasma cell pododermatitis due to renal and
hepatic amyloidosis.
DISCUSSION
In this study we identified a relatively large number
of cases of feline plasma cell pododermatitis in a short
period, despite this being a rare entity in the literature.1,3,7
All owners noticed asymptomatic ballooning of the
footpads, sometimes healing spontaneously, and only
when lesions became ulcerated, causing pain and reluc-
tance to walk were the cats referred to the practitioner.
Thus we propose that the true incidence of feline
plasma cell pododermatitis would be higher than
actually reported in the literature. We did not find sex,
breed, age or site predilections, similar to previous
reported data.1,3
We observed mitotic figures and binucleated plasma
cells, uncommon histological features in such a differ-
entiated population. In fact, plasma cells are considered
fully differentiated cells, representing the end-stage dif-
ferentiation of B lymphocytes, and hence not undergoing
further division. Binucleated and multinucleated human
plasma cells have been observed previously in cases of
myeloma,14 rheumatoid arthritis15 and in several oral
lesions.16 There is, however, some controversy con-
cerning the origin of these cells. Some authors found
nuclei and distinct apposing membranes, separated by
a gap, in pairs of closely apposed plasma cells, suggest-
ing that multinucleated plasma cells resulted from
fusion.17 Another study found no evidence of cellular
membranes in multinucleated plasma cells, suggesting
that the cells did not arise from fusion.15
Clinical follow-up revealed that both medical
(glucocorticoid therapy) and surgical treatments were
effective. No relapses occurred in follow-up periods of
at least 1 year. One cat died a few years after the
diagnosis of feline plasma cell pododermatitis because
of renal and hepatic amyloidosis, similar to a previous
report, which could be associated with plasma cell
disturbances.12
336 P. D. Pereira and A. M. R. Faustino

The localization of this entity to the footpads may
be related to close contact with external stimuli.
Nevertheless, the periodic recurrence of the disease and
the effectiveness of both medical and surgical treat-
ments, suggest that a local immunological dysfunction
may be the basis of feline plasma cell pododermatitis.
ACKNOWLEDGEMENTS
The authors wish to thank the Clnica Veterinria da
Areosa, Clnica Veterinria de Custias, Clnica Veter-
inria de Matosinhos, Vetconde and Policlnica Central
de Aveiro for their helpful contribution in collecting
data and for the clinical follow-up.
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swelling and ulceration in cats: a report of five cases.
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16. Yeo, J.F. Binucleated form of plasma cells in oral lesions
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Rsum Huit cas de pododermatite plasmocytes fline, vus sur une priode de 3 ans, ont t tudis par examen
histologique (hmatoxylline et osine), histochimique (methyl green-pyronin) et immunohistochimique
(anticorps contre la chaine lambda des immunglobilines). Aucune prdisposition de sexe, de race ou d'ge n'a
t observe. Aucune localisation de prdilection n'a t observe. La maladie a commenc dans tous les cas par
un gonflement des coussinets, suivi par une ulcration. L'examen histopathologique a montr la prsence de
plasmocytes en grand nombre, principalement localiss au niveau privasculaire. Des cellules binucles et des
figures de mitose ont t observes. Un suivi clinique pendant plus d'un an a montr une rmission complte
des lsions aprs traitement glucocorticode (4 cas) ou exrse chirurgicale (2 cas). Le suivi n'a pas t possible
dans un cas.

Resumen Se estudiaron ocho casos de pododermatitis plasmactica felina, recogidos durante un periodo de
tres aos, aplicando tcnicas de histologa, (hematoxilina y eosina), histoqumica (metil verde-pironina) e
inmunohistoqumica (anticuerpos contra cadena ligera lambda de inmunoglobulinas). No se observ predileccin
por sexo, raza, edad, o por una garra en particular. La enfermedad empezaba como una tumefaccin de las almo-
hadillas, seguida de ulceracin. Histolgicamente, las lesiones se caracterizaban por la presencia de un elevado
nmero de clulas plasmticas en un patrn predominantemente perivascular. Se observaron clulas plasmticas
binucleadas y figuras mitticas. El seguimiento clnico durante un ao revel una remisin total de las lesiones
tanto despus de la aplicacin de terapia glucocorticoidea (cuatro casos), como despus de la extirpacin quirrgica
(dos casos). No fue posible el seguimiento en un caso.

Zusammenfassung Acht Flle von ber einen Zeitraum von 3 Jahren gesammelter feliner Plasmazellpododer-
matitis wurden mit histologischen (Hmatoxylin-Eosin-Frbung), histochemischen (Methylgrn-Pyronin-
Frbung) und immunhistochemischen (Antikrper gegen Lambda-L-Ketten von Immunglobulinen) Techniken

2003 European Society of Veterinary Dermatology, Veterinary Dermatology, 14, 333337

 Feline plasma cell pododermatitis 337

untersucht. Es konnte keine Prdisposition hinsichtlich Geschlecht, Rasse, Alter oder Beteiligung der Pfoten
beobachtet werden. Die Erkrankung begann mit Schwellung der Fussballen gefolgt von Ulzerationen. Histologisch
waren die Lsionen durch das Vorhandensein einer grossen Anzahl von Plasmazellen mit einem vorrangig
perivaskulrem Verteilungsmuster charakterisiert. Zweikernige Plasmazellen und Mitosefiguren wurden beo-
bachtet. Klinische Verfolgsuntersuchungen ber den Zeitraum von mehr als einem Jahr zeigten totale Remission
sowohl nach Glukokortikoidtherapie in vier Fllen als auch nach vollstndiger chirurgischer Exzision bei zwei
Tieren. In einem Fall waren Verfolgsuntersuchungen nicht mglich.

2003 European Society of Veterinary Dermatology, Veterinary Dermatology, 14, 333337