7 0 S.S.

COUIAS, et al ANNALS OI GASTROENTEROLOGY 2003 16(1)70-73

Case eo/
Cowden's disease. A case report and review of the literature
S.S. Coulas
1
, D.C. Papaioannou
2
, Despina T. Papadeli
1
, D.J. Psilopoulos
1
, I.C. Ilefsiniotis
1
,
C.K. Maviogiannis
1
SUMMARY
Cowden's syndrome, or multiple hamartoma syndrome, is
a rare inherited disease with characteristic mucocutane-
ous lesions associated with multiple polyps of the gas-
trointestinal tract and abnormalities of the breast and thy-
roid gland. Cowden's disease carries a high risk of devel-
opment of malignancies, especially of breast and thyroid.
Rarely malformations and abnormalities occur in the skel-
etal system, central nervous system and urogenital tract.
Cowden's disease is included in the gastrointestinal (GI)
polyposis syndromes. Multiple, usually non-adenomatous
polyps throughout the GI tract, associated with skin and
oral papules and oesophageal glycogenic acanthosis are
considerd pathognomonic signs for diagnosis.
We present a case of a 48 yr-old Greek female with Cowden's
disease. The patient had facial papules, multiple GI hyper-
plastic polyps, oesophageal glycogenic acanthosis, goiter
and had developed breast cancer two years previous to di-
agnosis. Gastroenterologists have to be aware of and rec-
ognize this unusual clinical entity because of its correla-
tion with malignant tumors of the breast and thyroid.
Key words. Cowden`s disease, Hamaitoma, Hypeiplastic
polyp, PTIN gene, Castiointestinal polyposis syndiomes
INTRODUCTION
Cowden`s disease was fiist desciibed in 1963 by Iloyd
and Denis
1
. Since then appioximately 150 additional
cases have been iepoited in the liteiatuie. It is a iaie
autosomal, dominant, inheiited disease chaiacteiized by
multiple hamaitomas and neoplasms of ectodeimal, en-
dodeimal and mesodeimal oiigin affecting many oigans
and systems. Mucocutaneous lesions have been iepoit-
ed in the liteiatuie with a high fiequency (99-100%) and
aie the moste chaiacteiistic featuies of the disease. They
include multiple facial papules (tiichilemmomas), acial
keiatoses and oial papillomatosis
2,3
. Multiple hamaito-
mas and neoplasms of othei oigans, including thyioid
tumois (benign and malignant), fibiocystic disease of the
bieast, bieast caicinoma, neoplasms of the female geni-
tal tiact and gastiointestinal polyps have also been ie-
poited
3,4
.
Castiointestinal lesions aie fiequent (70-85%) in
patients with Cowden`s disease, though undeiestimated
in eailiei studies due to inadequate evaluation of the
alimentaiy tiact. Micioscopically, the most common find-
ings aie hypeiplastic polyps, hamaitomas and ganglion-
euiomas of the stomach and bowel, especially sigmoid
and iectum
5,6
. Recent genetic studies have shown associ-
ation with a geim line mutation of the PTIN gene (10q
22-23). The PTIN is a tumoi suppiessoi gene and its inac-
tivation incieases the iisk of bieast and thyioid cancei
7
.
In this iepoit we piesent a case of a 48 yeai-old Cieek
female with Cowden`s disease. We emphasize the endo-
scopic and histopathologic lesions of the CI tiact, piesent
a ieview of the liteiatuie and aleit the gastioenteiolo-
gists to considei the disease in the diffeiential diagnosis
of the gastiointestinal polyposis syndiomes.
1
Hea/oas/oen/eo|o, Un|/ Iacu|/, o| Nus|n A/|ens Un|ies|/,
Genea| Hos|/a| E|ena Ien|:e|ou A/|ens Geece
2
Pa/|o|o,
De/ H,e|a Hos|/a| A/|ens Geece
A!!ess |o coeson!ence
Di. S. Coulas, Hepatogastioenteiology Unit, Faculty of
Nuising, Univeisity of Athens,Ilena Venizelou Ceneial
Hospital, 2 Ilena Venizelou sq., 115 21 Athens, Cieece,
Tel. & fax: +3 210 6427379, e-mail: chiismav_otenet.gi
Cowden`s disease: A case iepoit and ieview of the liteiatuie 7 1
CASE REPORT
A 48-yeai-old female was admitted to the hospital
foi a lapaioscopic cholecystectomy foi cholelithiasis. Hei
symptoms weie not typical of a biliaiy colic (epigastiic
discomfoit, bloating) and she was iefeiied to the CI unit
foi clinical evaluation. Theie was a long histoiy of fibio-
cystic disease of the bieast and of a iight mastectomy, 2
yeais eailiei, foi an invasive bieast caicinoma.
One of hei sisteis has a histoiy of bieast cancei and
hei daughtei has von Recklinghausen`s disease.
The physical examination was notable foi isolated
multiple soft facial papules aiound the lips and eyelids.
The oial mucosa was noimal. Hei thyioid gland was en-
laiged and a iecent ultiasound had ievealed multiple
goitei. The thyioid function was noimal and autoanti-
bodies weie negative.
We peifoimed an uppei CI endoscopy which ie-
vealed extensive nodulaiity of the oesophagus, a mi-
ciopolypoid appeaiance of the stomach (body and an-
tium) and a duodenal ulcei. The second pait of the
duodenum was noimal. Biopsies weie taken fiom the
oesophagus and stomach. Histologic examination showed
glycogenic acanthosis of the oesophagus with mild oe-
sophagitis and mild chionic active gastiitis without atio-
phy and a laige load (giade 3) of Helicobactei pyloii
(Figuies 1, 2). In view of the miciopolypoid appeaiance
of the gastiic mucosa we went on to colonoscopy which
ievealed ovei 20 small polyps in the sigmoid and iec-
tum, ianging in size fiom 0,2 to 0,4cm in diametei. The
Figure 1-a. endoscopic image of multiple whitish nodules
thioughout the oesophagus.
Figure 2-b. histologic appeaiance of supeificial gastiic muco-
sa with mild active inflammation (H&I, x 100).
Figure 1-b. oesophageal mucosa showing mild inflammation
and glycogenic acanthosis (H&I, x 100).
Figure 2-a. endoscopic appeaiance of the miciopolypoid gas-
tiic mucosa.
7 2 S.S. COUIAS, et al
iest of the colon was noimal. Biopsies weie taken fiom
seven sigmoid and thiee iectal polyps. Histologically all
biopsies showed featuies of hypeiplastic-type colonic
polyp. Ciypts showed mildly distuibed oiientation and
mild focal mucous depletion. Seiiated boideis weie fo-
cally piesent but they weie not a piominent featuie of
the polyps. The lamina piopiia was oedematous with
mildly to modeiately dense inflammatoiy infiltiation by
lymphocytes, plasma cells and focally foamy histiocytes.
Occasional lymphoid follicles weie also piesent (Figuies
3a and 3b).
DISCUSSION
Cowden`s syndiome, oi multiple hamaitoma syn-
diome, is an unusual autosomal, dominant, inheiited
disease with chaiacteiistic mucocutaneous lesions com-
bined with gastiointestinal polyps and abnoimalities in
othei oigans with high fiequency of malignant tiansfoi-
mation, especially in the bieast and thyioid, but notably
not in the CI tiact
3,4
. The disease is associated with a
geim line mutation of the PTIN gene (10q 22-23)
7
. This
iaie clinical entity is well known to deimatologists and
stomatologists because mucocutaneous lesions aie the
most obvious and chaiacteiistic featuies of the disease
2-
4
.
CI lesions in Cowden`s disease include multiple polyps,
usually non-adenomatous, in the stomach, small and laige
bowel. The disease belongs to the spectium of polyposis
syndiomes togethei with Familial Adenomatous Poly-
posis (FAP), Heieditaiy Non Polyposis Colon Cancei
(HNPCC), Juvenile Polyposis and Peutz Jegheis syn-
diome
7,8
. In Cowden`s syndiome the polyps aie sessile oi
pedunculated and numbei fiom seveial to hundieds. The
most fiequent site of involvment is the sigmoid colon and
iectum. Most polyps aie hypeiplastic, lipomatous, gan-
glioneuiomatous, lymphoid and only occasionally ade-
nomatous. These polyps have a veiy low - if any - malig-
nant potential. The involvement of the oesophagus is
common in the foim of multiple whitish nodules, which
histologically coiiespond to glycogenic acanthosis
3,5,9,10
.
The combination of oesophageal glycogenic acantho-
sis with multiple non adenomatous CI polyps and muco-
cutaneous papules is consideied pathognomonic foi the
diagnosis of Cowden`s syndiome
5,11,12
.
Oui case is, to the best of oui knowledge, the fiist
documented case of Cowden`s disease in Cieece. The
patient was unawaie of hei disease as the skin lesions
weie diagnosed as veiiucae, the bieast cancei and thy-
ioid disease weie consideied and tieated independently
and theie was no suspicion of this unusual clinical entity.
She had multiple colonic hypeiplastic polyps and oesoph-
ageal glycogenic acanthosis, which is a pathognomonic
featuie, accoiding to the liteiatuie. The patient had al-
ieady developed iight bieast cancei and thyioid goitei.
Fuithei evaluation of the thyioid gland and a caieful
examination and follow up of the left bieast has been
advised. Some authois iecommend a piophylactic mas-
tectomy to pievent a second malignancy
12
. Clinical evalua-
tion of all fiist degiee ielatives is suggested as this is an
autosomal dominant inheiited disease.
Conclusively, the gastioenteiologists have to be awaie
and considei this iaie disease in the diffeiential diagnosis
of the gastiointestinal polyposis syndiomes. In a polypo-
Figure 3-b. histologic appeaiance of a hypeiplastic type sig-
moid polyp (H&I, x 100).
Figure 3-a. endoscopic appeaiance of the sigmoid colon with
multiple polyps.
Cowden`s disease: A case iepoit and ieview of the liteiatuie 7 3
sis syndiome the combination of mucocutaneous lesions
and oesophageal glycogenic acanthosis is consideied di-
agnostic of Cowden`s disease. Although CI lesions aie
benign and have no malignant potential it is ciucial to
identify these patients because the disease is inheiited
and caiiies a high iisk of malignancy of the bieast and
thyioid.
REFERENCES
1. Iloyd KM, Dennis M. Cowden disease. Ann Intein Med
1963: 48:136-142.
2. Staiink TM. Cowden disease. Analysis of fouiteen new
cases. J Am Acad Dematol 1984: 11:1127-1141.
3. Williaid W, Boigen P, Bol R, Tiwaii R, Osboine M.
Cowden disease: a case iepoit with analyses at the mo-
leculai level. Cancei 1992: 69:2969-2974.
4. Thyiesson HN, Doyle JA. Cowden disease (multiple
hamaitoma syndiome). Mayo Clin Pioc 1981: 56:179.
5. Kay P, Soetikno R, Mindelzun R, Young H. Diffuse Cly-
cogenic Acanthosis: An endoscopic maikei of Cowden
disease. Am J Castioenteiol 1997: 92:1038-1040.
6. Hizawa K, Iida M, Matsumoto T et al. Castiointestinal
manifestations of Cowden disease. Repoit of foui cases.
J Clin Castioenteiol 1994: 18:13-18.
7. Wiitzfeld DA, Petielli NJ, Rodiiguez-Bigas MA. Hama-
itomatous polyposis syndiomes: moleculai genetics, neo-
plastic iisk and suiveillance iecommendations. Ann Suig
Oncol 2001 May: 8:319-327.
8. Intius MM, Westeiman AM, van Velthuysen MI, Wil-
son JH, Hamilton SR, Ciaidiello FM et al. Moleculai and
phenotypic maikeis of hamaitomatous polyposis syn-
diomes in the gastiointestinal tiact. Hepatogastioentei-
ology 1999: 46:661-666.
9. Maiia C, Aimelao F, Vecchio FM et al. Cowden disease
with extensive gastiointestinal polyposis. J Clin Castio-
enteiol 1994: 18:42-47.
10. Coiensek M, Matko I, Scialovnik A. Disseminated he-
ieditaiy gastiointestinal polyposis with oiocutaneous
hamaitomatosis (Cowden syndiome). Indoscopy 1984:
16:59-63.
11. Iasshnei BA, Ridell RH, Winans CS. Canglioneuioma-
tosis of the colon and extensive glycogenic acanthosis in
Cowden disease. Dig Dis Sci 1986: 31:213-216.
12. Walton BJ, Moiain WB, Baughman RD. A fuithei indi-
cation foi piophylactic mastectomy. Suigeiy 1986: 99:82-
86.