The Journal of Laryngology & Otology

March 2002, Vol. 116, pp. 221–223

Cowden’s disease: a rare cause of oral papillomatosis

Marissa Botma, F.R.C.S., Derrick I. Russell, F.D.S., R.C.S.* , Robin A. Kell, F.R.C.S.

Abstract
Cowden’s disease is a rare autosomal dominant condition with characteristic mucocutaneous papillomatous
lesions. These lesions are mucocutaneous markers for increased risk of malignancies in the thyroid, breast and
the gastrointestinal tract. We discuss the case of a 50-year-old female patient who presented with oral and
cutaneous papillomoas and a past history of breast malignancy. Important management aspects of these patients
are considered.
Key words: Mouth Diseases; Skin Diseases; Papilloma; Neoplastic Syndromes; Hereditary

Introduction
Cowden’s disease is a rare disorder affecting the skin and
mucous membranes, inherited as an autosomal dominant
trait with incomplete penetrance and variable expression.1
It was Žrst described in 1963 by Lloyd and Dennis and
named after the affected patient, Rachel Cowden.2
The disease is characterized by multiple papillomas of
the skin and oral mucosa, multiple benign tumours of the
internal organs and a signiŽcant increased risk of devel-
oping breast carcinoma as well as malignancies of the colon
and thyroid.3 The cutaneous lesions that are present in
99–100 per cent of cases are striking and because they
precede the development of cancer by several years, serve
as important clinical markers for identiŽcation of patients
at high risk for malignancies of the breast or thyroid.4

Case report Fig. 1

This 50-year-old female presented to our clinic with Papillomatous lesions on the gingiva.
extensive oral papillomatosis interfering with the Žtting
of her dentures. These lesions had been present for 10 to
15 years without any discomfort or problems with
mastication or speech.
She had a history of breast carcinoma that had required
a mastectomy 18 years ago. She suffered from epilepsy for
which she took phenytoin. She also had a history of
thyroiditis, which left her hypothyroid, for which she took
thyroxine.
Clinical examination of the oral cavity revealed multiple
papillomatous lesions on the mucosa of the upper and
lower gingiva (Figure 1), anterior dorsum of tongue
(Figure 2), left anterior tonsillar pillar and posterior
pharyngeal wall. The lesions were greater than 3–4 mm
in size. No other lesion was noted on mucosal surfaces. Her
facial skin revealed numerous pedunculated soft papules
consistent with achrochordons.
Blood analysis revealed her to be vitamin B12 and iron
deŽcient. She was investigated with an upper gastrointest-
inal endoscopy and colonoscopy. These showed several
polyps in the stomach mainly in the pre-pyloric area and Fig. 2
the duodenum. The histology was consistent with hyper- Papillomatous lesions on the anterior dorsum of tongue.

From the Departments of Otolaryngology and Oral and Maxillofacial Surgery* , Victoria InŽrmary, Glasgow, UK.
Accepted for publication: 18 September 2001.

221
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plastic polyps. Colonoscopy revealed a collection of polyps
in the splenic exure and biopsies showed features of a
mucosal neuroma.
Treatment consisted of laser excision of the multiple
polyps in the oral cavity. The histology showed Žbro-
epithelial polyps with orid epithelial hyperplasia. There
was no evidence of dysplasia or malignancy. She was also
started on folic acid and iron supplements and regular
follow-up has been arranged especially regarding her
intestinal lesions.
Discussion
Cowden’s disease or multiple hamartoma and neoplasm
syndrome is a rare genodermatosis of autosomal dominant
inheritance with variable expression.5 A positive family
history is present in half of the patients reported to date.
Symptoms usually appear during the second and third
decade of life.6
The cause of Cowden’s disease remains unknown. Many
genetic studies have been performed to identify the cause
of this syndrome, including chromosome analysis, DNA
repair studies, HLA typing, immunoglobulin allotyping
and gene and oncogenes. Recently, a series of germline
mutations have been identiŽed from Cowden’s syndrome
families in a gene known as PTEN/MMAC1/TEP1. These
data conŽrm the observation that mutations of the gene
coding sequence are responsible for at least some cases of
Cowden’s syndrome and further deŽne the spectrum of
mutations in this autosomal dominant disorder.7 Viral
infection has been suggested as a cause, but no recent
study supports this hypothesis. It has also been suggested
that impaired immunodeŽciency, including diminished
natural killer (NK) cell activity and abnormal ratio of
helper to suppressor T lymphocytes play a role by
impairing the cell-mediated immune response to tumour
cells.8
Cowden’s disease mainly affects Caucasians (96 per
cent) and is most common in females (60 per cent). The
age of onset ranges from four–75 years (mean 39 years).9
Mucocutaneous lesions are most commonly observed
and are present in almost all reported cases. The oral
lesions are either discrete, smooth or verrucous papillo-
mas, 1–3 mm in diameter found anywhere on oral mucosa
but more common on labial, palatal and gingival surfaces
or coalescent papules, giving a cobblestone appearance,
found mainly on the tongue dorsum, buccal mucosa and
oropharynx.9 These lesions should be differentiated from
other mucocutaneous pathology (Table I). Of interest to
the otolaryngologist is the involvement of pharyngeal and
laryngeal lesions as previously described in the literature.1 0
The cutaneous lesions consist of multiple skin coloured
papules and small nodules 1–4 mm in diameter found
mainly on the eyelid, glabella, pinna, nasolabial folds,
mouth and lateral neck. The second most common skin
TABLE I
differential diagnosis of oral lesions
Multiple condylomata acuminata
Multiple traumatic Žbromas
Multiple neuromas
Acanthosis nigricans
Darier’s disease
Heck’s disease
Phenytoin hyperplasia
Tuberous sclerosis
Lymphangioma
Pyogenic granuloma
Squamous cell carcinoma
m. botma, d. i. russell, r. a. kell
lesion is acral keratosis which consist of non-speciŽc esh
coloured, at-topped, smooth or rough papules found
mainly on the dorsum of hands and feet.1
A common internal manifestation of Cowden’s syn-
drome is thyroid disease (67 per cent) which consists
mainly of goitre, adenoma and follicular carcinoma.1 1
Other lesions include foetal adenocarcinoma, oncocytoma,
thyroid hyperfunction, thyroiditis and thyroglossal duct
cysts.1 2 Breast lesions are present in 85 per cent of the
female patients, including carcinoma of the breast (36 per
cent).4 Other breast lesions include Žbro-adenomas,
Žbrocystic disease, duct papillomas or adenocarcinoma.1 ,1 1
Gastrointestinal lesions (71 per cent) consist of multiple
polyps that may be encountered anywhere in the gastro-
intestinal tract. The polyps may be haematomatous,
juvenile lipomatous, lymphomatous, inammatory, hyper-
plastic or occasionally adenomatous lesions.1 3
Abnormalities of the genito-urinary system presenting
as menstrual irregularities, ovarian cysts and endometrious
carcinoma have been described in 55 per cent of patients.9
Skeletal abnormalities are seen in about one third of
patients with Cowden’s disease and these include, mild
vertebral curvature abnormalities, craniomegaly, pectus
excavatum and a high arch palate.1
A miscellaneous group of conditions may be associated
with Cowden’s disease. Some patients have ocular
abnormalities such as hypertelorism, lenticular opacities,
congenital vascular anomaly of the fundus, glaucoma and
occasionally glioma.5 Others have abnormalities of the
nervous system, including neuromas of cutaneous nerves,
neuroŽbroma, meningioma, Lhermitte Duclos disease and
hearing loss.1 4 Cardiorespiratory abnormalities include
hypertension, atrial septal defect (ASD), mitral valve
prolapse and aortic mitral valve insufŽciency, as well as
pulmonary hamartomas.5 Other tumours reported include
lipoma, liposarcoma, non-Hodgkin’s lymphoma, transi-
tional cell carcinoma of the bladder and Merkel cell
carcinoma. 9
The histological features of the cutaneous lesions
include features similar to hair follicle hamartomas,
showing a pattern of tricholemmomas, namely islands or
cords of layered glycogen-rich epithelial cells surrounded
by single layers of smaller palisade cells.2 Dermal inŽltrates
of mononuclear cells include Langerhans cells, macro-
phages and numerous mast cells. Oral lesions show a
Žbrovascular cord surrounded by hypoplastic epithelium
with a slight hyperparakeratosis consistent with Žbro-
epithelial polyps.1
TABLE II
diagnostic criteria for cowden’s disease15
A Major criteria:
1. Cutaneous facial papules
2. Oral mucosal papillomata
B Minor criteria:
1. Acral keratosis
2. Palmoplantar keratosis
C Family history of Cowden’s disease
DeŽnitive diagnosis
1. Two major criteria
2. One major and one minor criterion
3. One major criterion and family history of Cowden’s
disease
4. Two minor criteria and family history of Cowden’s
disease
Probable diagnosis
1. One major criterion
2. One minor criterion and a family history of Cowden’s
disease
clinical records
The diagnosis of Cowden’s disease is made of clinical
features as proposed by Salem and Steck in 1983. They
describe major criteria, minor criteria and family history.1 5
The diagnosis can be considered deŽnite or probable by
using these criteria (Table II). The histological features of
biopsies taken from lesions would also re-inforce the
clinical suspicion by excluding other possible causes.
Treatment of the oral lesions may include bleomycin
chemotherapy, radiotherapy (Iridium 192) and surgical or
carbon dioxide laser debulking. Interferon (alpha) 2a may
also be used.1 6
The prognosis of Cowden’s disease is poor because of
the high risk of developing malignancies and for this
reason these patients should be screened for occult
malignancies and a regular follow-up schedule should be
employed.1 7
Conclusion
Our patient, as well as demonstrating the oral and skin
manifestations, also had a history of thyroiditis, breast
carcinoma and gastrointestinal polyps.
The increased size of the oral lesions compared with
other descriptions may well be due to the fact that she was
taking phenytoin, which is commonly associated with
gingival hyperplasia.
Cowden’s disease is an uncommon cause of mucocuta-
neous papillomatosis but because this precedes the
development of cancer by several years, they serve as
important clinical cutaneous markers for identiŽcation of
patients at high risk for malignancies, in particular, of the
breast or thyroid.
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Address for correspondence:
Ms Marissa Botma,
Department of Otolaryngology,
Great Ormond Street Hospital for Children,
London WC1N 3JH, UK.
Fax: 1 44 (0)207 8298644
E-mail: mbotma@doctorsworld.com
Ms M. Botma takes responsibility for the integrity of the
content of the paper.
Competing interests: None declared