Veterinary Dermatology 2005, 16, 346 350

Case report

Blackwell Publishing, Ltd.

Isotretinoin in the treatment of multiple benign pilomatrixomas

in a mixed-breed dog
STEFANO TOMA and CHIARA NOLI
Ospedale Veterinario Cuneese, Via Cuneo 52/N, 12011 Borgo S. Dalmazzo (CN), Italy
(Received 3 February 2005; accepted 19 July 2005)

Abstract An 18-month-old cross-breed dog developed multiple skin nodules, which over 8 months had
increased in size and number. Biopsy samples were submitted for histopathological examination and revealed
multiple benign pilomatrixomas. The dog was treated with 1 mg kg1 isotretinoin daily, which led to a stabilization of the size and number of the lesions. Attempts to lower the dosage to an every other day regimen led to an
increase in the nodules size and number. Monthly complete blood count and chemistry tests and Schirmer tear
tests were performed to monitor any adverse effects of the retinoid treatment. No adverse effects were noted. To
the authors knowledge, this is the first report of multiple pilomatrixomas arising in a young dog and successfully
controlled with oral retinoids.

I NTRO D U CTI ON

C A S E R E P O RT

Pilomatrixoma is an uncommon follicular tumour

that is thought to arise from the matrical cells of the
hair bulb and has been described in dogs, cats and
human beings.13 In dogs, pilomatrixomas account
for about 1% of all cutaneous neoplasias, 3% of all
epithelial skin tumours and 1319% of all follicular
tumours.4 6 Breed predisposition has been described,
including Kerry blue terriers, soft-coated Wheaton
terriers, Bouvier des Flandres, Bichon frise, standard
poodle, Bedlington terriers and schnauzers.4,6 Tumours
are usually solitary, although rarely multicentric
cases have been observed.6 Therapy of pilomatrixoma
is surgical excision, cryotherapy or observation
without treatment.1,6 To the authors knowledge, no
pharmacological therapy has ever been described for
this tumour.
Retinoids are natural or synthetic derivatives of
vitamin A used in dermatology for the treatment of
a variety of epidermal and follicular diseases. Isotretinoin, an isomer of retinic acid, was successfully
used for the pharmacological therapy of multiple benign
cutaneous adnexal tumours.7 The purpose of this
case report is to describe a dog diagnosed with multiple
benign pilomatrixomas medically managed with oral
isotretinoin.

Case history

Correspondence: Chiara Noli, Ospedale Veterinario Cuneese, Via

Cuneo 52/N, 12011 Borgo S. Dalmazzo (CN), Italy. E-mail:
pitnoli@iol.it
346

A 30-kg 2.5-year-old intact male collieGerman

shepherd cross dog was presented for dermatological
evaluation with an 8-month history of multiple skin
nodules. Some of these nodules had previously been
excised by the referring veterinarian; however, histopathology was not performed. New nodules had developed over time. Mild pruritus was associated with
ulceration of some of the lesions, and a 7-day course of
enrofloxacin (unknown dosage) had not led to any
improvement.

Clinical and histological findings

On general physical examination, the dog appeared
in excellent health. On dermatological examination, 13
intradermal or subcutaneous nodules of varying diameters (0.57 cm) were observed. The lesions appeared
round, well circumscribed, mobile, solid, and were
not painful on palpation. They were located over the
whole body, particularly on the head, neck and trunk
(Figs 13).
Differential diagnoses included bacterial or fungal
granulomas, multiple histiocytic proliferations, neoplasms
arising from the hair follicole (e.g. trichoblastomas,
pilomatrixomas), mast cell tumours, multicentric cutaneous lymphoma and other tumours. Complete blood
counts and serum biochemical analyses were within
normal limits. No abnormalities were detected on
thoracic radiography. Bacterial and fungal cultures
of material obtained from two nodules by fine-needle
aspiration were performed and yielded no microorganisms. A cytological examination of samples obtained
by fine-needle aspiration from several nodules showed
2005 European Society of Veterinary Dermatology

Canine multiple pilomatrixoma and isotretinoin

347

Figure 1. A 7-cm large alopecic and ulcerated nodule on the right

shoulder of a mixed-breed dog affected by multiple pilomatrixomas.

Figure 3. A 3-cm large alopecic and ulcerated nodule on the ventral

neck of a mixed-breed dog affected by multiple pilomatrixomas.

Figure 2. A 0.7-cm large alopecic nodule on the upper right lip of a

mixed-breed dog affected by multiple pilomatrixomas.

a limited number of cells. In some samples, a moderate

amount of amorphous keratin was observed.
Two nodules were excised under general anaesthesia
and examined histologically. Samples were processed,
sectioned and stained with H&E following standard
procedures. In both, several cystic cavities full of keratin and lined by epithelium were observed (Fig. 4). The
keratin within the cavities was an amorphous, matrical
type, with ghost cells. The epithelial cells lining the
cavities were small, rounded, basophilic in several
layers, and characterized by abrupt keratinization
(absence of trichohyalin or keratohyalin granules). Both
nodules were diagnostic of benign pilomatrixoma, were
well circumscribed and completely excised.

Therapy and follow-up

The largest nodules were surgically excised. However,
new nodules had continued to appear since the first
examination, just 2 months prior to the surgical excision. In addition, the nodules that were present had
steadily increased in size. Treatment options for this
dog were repeated surgical excisions or pharmacologi-

Figure 4. Histopathology of pilomatrixoma: several intradermal

cysts filled with amorphous keratin with ghost cells surrounded by a
wall of epithelial cells with abrupt keratinization and matrical
differentiation. H&E, 10.

cal therapy. The latter was chosen by the owner and

treatment with 1 mg kg1 per day of oral isotretinoin
(Roaccutan, Roche Spa, Milano, Italy) was initiated.
Suggested dosages for retinoids in dogs range from 1 to
3 mg kg1 once or twice daily.7 A higher dose may have
been more effective but was considered too expensive
by the owner.
Two months after the initiation of isotretinoin therapy, only one new small nodule had appeared and the
tumours that were already present had not increased in
size. At this point the dosage was decreased to 1 mg kg1
every other day. After 1 month of alternate day

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348

S Toma and C Noli

therapy, several new nodules had appeared and the

nodules previously present had increased in size. The
daily dosage regimen was re-introduced and lesions
stopped increasing in size. No new lesions appeared for
the following 6 months. Since initiating the therapy,
complete blood counts and serum biochemical analyses (including liver enzymes, triglycerides and cholesterol) were monitored monthly. Results of these tests
were always within normal limits. Schirmer tear tests
were also performed monthly, and no abnormalities in
tear production were noted. Currently the dog has nine
small nodules, which have not increased in size since
the beginning of the therapy (9 months ago).

D ISCU SSIO N
In this report, a case of pilomatrixoma that responded
to medical therapy with oral retinoids is described.
Pilomatrixoma is a benign skin tumour arising from
the matrix of the hair bulb.1 Usually, it occurs as a
solitary, well-encapsulated, sometimes ulcerated dermal
and/or subcutaneous nodule.6 In humans, this tumour
occurs predominantly in children.3 In dogs, the age of
onset for pilomatrixoma may be as young as 1 year,
with an average age of onset of 6.5 years.6 The dog in
this report was 1.5 years of age, younger than the average for the development of this disease. In humans,
occasionally multiple lesions are reported and are
considered inherited as an autosomal dominant condition.3 Because of the age of onset and wide distribution
of lesions, a congenital or inherited defect is suspected.
Currently, there is no published report in veterinary
medicine to confirm this hypothesis.
Canine pilomatrixomas are usually 110 cm in
diameter, frequently ulcerated, and show predilection
for the neck, shoulders, back and tail.1,5,6 In our case,
the nodules were 0.57 cm in diameter and the larger
ones were ulcerated. Lesions in this case were mainly
located on the head, neck, thorax and back, in accordance with previous reports. Furthermore, the dog in
this report had nodules noted on the lateral and medial
aspect of the left foreleg. Interestingly in humans, the
upper limbs, face and neck are considered predilection
sites.3
Cytological features of samples obtained by fineneedle aspiration from pilomatrixomas include high
cellularity and numerous clusters of basaloid cells with
evenly distributed chromatin and small distinct nucleoli surrounding sheets of ghost cells (fully keratinized
cells with a visible unstained nucleus).8 Amorphous
keratinized material can also be observed.8 In our case,
the cytological examination of samples obtained by
fine-needle aspiration revealed the presence of amorphous keratin, but significant amounts of epithelial
cells were not present. This may be because of the fact
that the cytological sample was probably obtained from
the centre of large cysts filled with keratin, which were
present in the nodules sampled. The presence of amorphous keratin and the absence of significant amounts

of other types of cells are suggestive of the diagnosis of

a follicular tumour. These results support the exclusion
of other differentials, such as round cell proliferations
or inflammatory granulomas. This highlights the
importance of performing a cytological examination of
every skin nodule before its surgical excision.
Pilomatrixomas are histologically characterized by
multiple cysts, formed by thick walls of small basophilic
basaloid cells with abrupt keratinization that surround
a central area of pink amorphous keratin with ghost
cells.1,2 Calcification and granulomatous inflammation due to free keratin in the dermis are frequently
seen. In our case, the histological findings of multiple
cysts in the dermis, filled of amourphous keratin with
ghost cells, were diagnostic of pilomatrixoma. Cysts
were surrounded by a thick wall of epithelial basaloid
cells with matrical differentiation, characterized by
abrupt keratinization (absence of trichohyalin or keratohyalin granules). Calcification was not observed in
any of the sections.
Malignant pilomatrixomas can be differentiated
from benign pilomatrixomas on histopathology by a
higher nuclear pleomorphism and atypia of cells and
by the finding of lymphatic invasion of the tumour
cells.1,6 Lymph node, lung, nervous system and bone
metastases have been reported.6,911 Despite the wide
lesion distribution and constant development of new
lesions in this case, we did not consider the neoplasias
in our dog to be malignant. Factors that support the
diagnosis of benign pilomatrixoma include the lack of
clinical and histological features of malignancy (e.g.
distant metastases, cellular atypia or lymphatic invasion),
young age of onset and prolonged survival (e.g. 1.5 years
after the onset of the disease, the dog of this report is
still alive and in excellent general health).
Most authors describe benign pilomatrixomas as
solitary tumours and mention the rare occurrence of
multiple neoplasias.1,6 To the authors knowledge,
there is no published report of multicentric benign
pilomatrixomas. One anecdotal report by Vercelli and
Taraglio describes a case similar to ours.12 The authors
reported an 8-year-old briard with a 2-year history of
recurrent and multiple pilomatrixomas. The nodules
were 18 cm in diameter, with variable ulceration,
and without metastases to lymph nodes or lungs. The
authors reported that 20% of the tumours recurred
3 months after surgical excision and that new nodules
developed, leading the owner to opt for euthanasia.
Retinoids are natural or synthetic derivatives of
vitamin A used in dermatology for the treatment of a
variety of epidermal and follicular diseases. In human
medicine, they are administered for diseases such as
cystic acne, pityriasis, Darier disease, psoriasis and
lamellar ichthiosys.13,14 In veterinary medicine, retinoids have been used for the treatment of feline chin
acne, idiopathic nasal hyperkeratosis, ear margin
dermatosis, acanthosis nigricans, schnauzer comedo
syndrome, sebaceous adenitis, congenital lamellar
ichthyosis, idiopathic seborrhea, multiple keratoacanthomas, squamous cell carcinoma and epitheliotropic

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Canine multiple pilomatrixoma and isotretinoin

lymphoma.1520 Their mechanism of action is mediated
by membrane, cytoplasmatic and nuclear receptors as
they modulate mRNA, prostaglandins and protein
synthesis. In addition, retinoids regulate the expression
of keratins in the epithelial cell and formation of the
cornified cell envelope. Retinoids thus have the ability
to regulate proliferation, growth and differentiation of
keratinocytes.1315,19
Isotretinoin, an isomer of retinic acid, is effective in
the treatment of primary defects of hair follicles and
of sebaceous glands.15 It is used at the dosage of
13 mg kg1 every 1224 h, and therapy is usually
administered for 3 or 4 months until clinical remission
is obtained. Frequently it is continued as maintenance
therapy, at 50% of the original dose or less for life.7,19
Isotretinoin has been successfully used for the
pharmacological therapy of multiple benign cutaneous
adnexal tumours, such as multiple intracutaneous
cornifying epitheliomas (keratoacanthomas, ICE),15,18,21
inverted papilloma,18 sebaceous adenomas18,22 and
epidermal cysts.18 For this reason, isotretinoin was
chosen as pharmacological therapy of multiple benign
pilomatrixomas. In this case, isotretinoin was effective
in preventing new lesions from forming and the present
nodules from progressing at the dosage of 1 mg kg1
per day. A complete remission of the lesions could not
be achieved. The dosage of retinoids used in our dog
was at the lower end of previously suggested doses, as
a result of financial constraints. Possibly, a partial or
complete clinical remission of the existing nodules
could have been achieved with higher doses. However,
in order to determine the efficacy of this treatment in
stopping the progression of multiple benign pilomatrixomas, more cases would need to be evaluated. Of
the seven dogs with ICE described by White and coworkers,18 only five were successfully treated with retinoids
(isotretinoin or etretinate). One out of three dogs treated
with isotretinoin responded well, whereas the others
only partially responded.
Side effects of retinoids are common in human
beings.23 These include cheilitis, xerosis, keratoconjunctivitis sicca, pruritus and facial dermatitis,
thinning and loss of hair, palmo-plantar scaling, sight
alteration, high liver enzyme serum levels, bone pain,
skeletal abnormalities, myopathies, abortion and teratogenic effects. In dogs, retinoids are usually well tolerated. The most frequent side effects in dogs include
elevation of serum liver enzymes and serum lipids, and
keratoconjunctivits sicca.15,17,19 For these reasons, it is
useful to monitor liver enzymes and lipids and tear
production with a Schirmer test on a monthly basis.
No side effects of retinoid treatment were observed in
this case.
We conclude that oral isotretinoin administration
may be an effective treatment for the control of multiple
benign pilomatrixomas. In this case report, retinoids
appeared to prevent new nodule formation and the
progression of existing lesions. It may thus be considered a possible alternative to repeated surgical excision
of the lesions or euthanasia.

349

AC K N OW L E D G E M E N T S
The authors would like to thank Dr Irene Bertoldo
for referring this case and Dr Natalie Perrins for the
English review of this article.

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cutaneous neoplasia and cutaneous lymphoma in dogs.

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Rsum Un chien croisg de 18 mois a dvelopp de nombreux nodules cutans, qui ont augment de taille
et en nombre en 8 mois. Des biopsies ont montr des pilomatrixomes multiples bnins. Le chien a t trait avec
1 mg kg1 disotretinoine par jour, ce qui a permis une diminution du nombre et de la taille des lsions. Des analyses sanguines et un test de Schirmer mensuels nont pas montr danomalie. A la connaissance des auteurs, il
sagit de la premire description clinique de pilomatrixomes chez le jeune chien rpondant un traitement avec
les rtinodes.
Resumen Un perro de raza mixta de 18 meses de edad desarroll numerosos ndulos en la piel, que a lo largo
de ocho meses haban crecido en tamao y nmero. Se tomaron biopsias para el estudio histopatolgico
resultando en un diagnstico de pilomatricomas benignos. El perro recibi tratamiento diario con isotretinona
a 1 mg /kg, resultando en una disminucin del nmero y tamao de los ndulos. Los intentos de disminuir la dosis
a un rgimen de das alternos producan un empeoramiento clnico que se manifestaba con los ndulos
aumentando en tamao y nmero. Para vigilar reacciones adversas al tratamiento con retionides, cada mes se
realizaron recuentos completos de sangre y bioqumica sangunea, as como la prueba de Schirmer para evaluar
la produccin de lgrimas. No notamos ningn efecto adverso. Segn indican nuestras revisiones, este es el primer
caso descrito de mltiples pilomatricomas en un perro joven y su control con retinoides va oral.
Zusammenfassung Ein 18 Monate alter Mischlingshund entwickelte multiple Hautknoten, die ber einen
Zeitraum von acht Monaten an Gre und Anzahl zugenommen hatten. Biopsieproben wurden fr eine histopathologische Untersuchung eingeschickt und zeigten multiple gutartige Pilomatrixome. Der Hund wurde mit
1 mg kg1 Isotretinoin tglich behandelt, was zu einer Abnahme der Gre und Anzahl der Lsionen fhrte. Versuche die Dosierung auf jeden zweiten Tag zu verringern, fhrte zu einer Zunahme der Gre und Anzahl der
Knoten. Monatliches Blutbild und chemische Blutuntersuchungen sowie Schirmer Trnen Tests wurden durchgefhrt, um eventuelle Nebenwirkungen durch die Behandlung mit Retinoiden zu berwachen. Keinerlei Nebenwirkungen wurden festgestellt. Soweit dem Autor bekannt, ist dies der erste Bericht von multiplen
Pilomatrixomen, die bei einem jungen Hund auftraten und mit oralen Retinoiden erfolgreich kontrolliert wurden.

2005 European Society of Veterinary Dermatology, Veterinary Dermatology, 16, 346 350