BACKGROUND: The Muir-Torre syndrome is a rare autosomal dominant condition and is currently considered a subtype of the more common hereditary nonpolyposis colorectal cancer syndrome, in which multiple primary malignancies occur together with sebaceous gland tumors. CASE PRESENTATION: We describe a case of a 62-year-old woman with three primary colorectal tumors, genital tumor, and sebaceous adenomas and present her family history of three generations. Our case represents the first case reported from Greece in the international literature. CONCLUSION: Recognition of the syndrome in patients with sebaceous gland tumors should facilitate early detection of subsequent malignancies if the patient is entered into appropriate screening programs

Angelopoulos, S

Betsis, D

Blouhos, K

Tsachalis, T

Tsalis, K

Vasiliadis, K

English

PubMed

K Tsalis

K Blouhos

K Vasiliadis

T Tsachalis

S Angelopoulos

D Betsis

Springer - Publisher Connector

BioMed Central
World Journal of Surgical Oncology
ssOpen AcceCase report
Sebaceous gland tumors and internal malignancy in the context of 
Muir-Torre syndrome. A case report and review of the literature
K Tsalis*, K Blouhos, K Vasiliadis, T Tsachalis, S Angelopoulos and D Betsis
Address: Fourth Department of Surgery, Aristotle University of Thessaloniki, Greece
Email: K Tsalis* - ctsalis@med.auth.gr; K Blouhos - kostasblu@hotmail.com; K Vasiliadis - keva@med.auth.gr; 
T Tsachalis - seneka21@med.auth.gr; S Angelopoulos - con@the.forthnet.gr; D Betsis - keva@med.auth.gr
* Corresponding author    
Abstract
Background: The Muir-Torre syndrome is a rare autosomal dominant condition and is currently
considered a subtype of the more common hereditary nonpolyposis colorectal cancer syndrome,
in which multiple primary malignancies occur together with sebaceous gland tumors.
Case presentation: We describe a case of a 62-year-old woman with three primary colorectal
tumors, genital tumor, and sebaceous adenomas and present her family history of three
generations. Our case represents the first case reported from Greece in the international
literature.
Conclusion: Recognition of the syndrome in patients with sebaceous gland tumors should
facilitate early detection of subsequent malignancies if the patient is entered into appropriate
screening programs.
Background
Distinguishing cutaneous signs, which are associated with
hereditary cancer syndromes, are known as cancer-associ-
ated genodermatoses. The Muir-Torre syndrome (MTS) is
an example, and is defined by the combination of at least
one sebaceous adenoma, epithelioma or carcinoma and
at least one visceral carcinoma occurring in the same indi-
vidual in the absence of other precipitating factors such as
radiotherapy or AIDS [1]. Individuals with the syndrome
may develop multiple primary malignancies at different
sites. Diagnosis of MTS has implications for cancer screen-
ing and surveillance in the affected individual and his or
her relatives [2,3]. Our case represents the first case
reported from Greece in the international literature.
Case presentation
A 62-year-old woman with a past history of adenocarci-
noma of the rectum and genital cancer, underwent
abdominoperineal resection with a permanent left
ostomy and total hysterectomy in the age of 37. Some 9
years later she was found to have colonic polyps with
malignant transformation and was treated by surgical
resection (colotomy and polypectomy).
In 1993 and 1997 she was found to have benign colonic
polyps which were excised endoscopically, and in March
and June 2003 she was referred to our surgical outpatient
department with subcutaneus lesions, first on the left side
of the abdominal wall and then on the right buttock. The
lesions were excised under local anesthesia and were
reported to be sebaceous adenomas, and the diagnosis of
the Muir-Torre syndrome (MTS) was suggested. Ever since
Published: 08 February 2006
World Journal of Surgical Oncology 2006, 4:8 doi:10.1186/1477-7819-4-8
Received: 14 September 2005
Accepted: 08 February 2006
This article is available from: http://www.wjso.com/content/4/1/8
© 2006 Tsalis et al; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 4
(page number not for citation purposes)
World Journal of Surgical Oncology 2006, 4:8 http://www.wjso.com/content/4/1/8the patient was commenced on surveillance program that
included annual clinical examination, CEA evaluation,
chest radiography, urine cytology, colonoscopy and mam-
mography.
In June 2005, an adenocarcinoma of the ascending colon
was detected. An abdominal computed tomography (CT)
scan showed no evidence of metastatic disease or paraaor-
tic lymphadenopathy. A right hemicolectomy was per-
formed, and the pathology report confirmed a poorly
differentiated mucinous adenocarcinoma (stage II,
T3N0M0, Dukes B). Screening tests for further malignan-
cies, including chest radiography and upper GI endoscopy
were all negative, and none of the tumor markers were ele-
vated.
The patient has twin sons both of whom are in their early
forties and currently healthy. She had three siblings from
that only one brother is alive without cancerous history.
One brother underwent a subtotal gastrectomy in his for-
ties for gastric cancer and died in his fifties of a meta-
chronous primary gastric cancer in the oesophagogastric
junction. Another brother is alive, who has undergone a
colon resection twice, first in his twenties and then 22
years later for colon cancer, and has a history of multiple
sebaceous adenomas. Her mother had undergone a colon
resection in her forties for colon cancer and developed at
least seven primary cancers of colon, genitourinary, upper
GI tract, sebaceous adenomas-epitheliomas, during a 21-
year period. She died in her sixties of a second gastric can-
cer. Her grandfather died in his forties from colon cancer.
Further family history is less clear, but the patient believes
that some other members of her family died of cancers at
various sites. Ages at diagnosis of cancer ranged from 29
to 62 years (median age: 48 years).
All family members were suggested to undergo endoscopy
and dermatological surveillance. A pedigree of four family
generations is shown in Figure 1.
Discussion
The Muir-Torre syndrome was independently described
by Muir in 1967 and Torre in 1968, and has since been
recognized as a subtype of Lynch Type II hereditary non-
polyposis colon cancer (HNPCC) [4,5]. Akhtar et al in
their review study identified a total of 205 reported cases
in the world literature [6]. In the same study the authors
reported that the defining feature of this syndrome is the
combination of sebaceous gland tumors and at least one
visceral cancer, usually gastrointestinal or genitourinary
carcinomas.
Clinically the diagnosis of MTS is based on the presence of
at least one sebaceous gland tumor associated with at least
one primary visceral malignancy, as it happened in our
case. Alternatively, diagnosis of the syndrome can be
made if the patient has multiple keratoacanthomas with
multiple internal malignancies and a family history of
MTS [7]. Muir-Torre syndrome can also be diagnosed by
genetic testing. A high proportion of tumors from MTS
patients show microsatellite instability (MSI) due to
germline mutations in either of two DNA mismatch repair
(MMR) proteins [8].
Typical skin tumors associated with this syndrome
include sebaceous adenomas, epitheliomas and carcino-
mas. Keratoacanthomas and basal cell carcinomas with
sebaceous differentiation may also occur. All these seba-
ceous gland tumors are rare in the general population and
the finding of such a tumor may represent a marker for
MTS and should prompt a search for occult malignancy
[9]. In addition, fifty-six per cent of skin lesions in MTS
occur after diagnosis of the first malignancy, 6% occur
concomitantly and 22% of skin lesions occur as the first
Condensed pedigree of four generations (I to IV) of the fam-ilyFigur  1
Condensed pedigree of four generations (I to IV) of the fam-
ily. Patients II-2 and III-2 had four and three primary gastric 
and colorectal carcinomas respectively, as well as other 
forms of cancer. Squares: men, circles: women, diamonds: per-
sons of either sexPage 2 of 4
(page number not for citation purposes)
World Journal of Surgical Oncology 2006, 4:8 http://www.wjso.com/content/4/1/8malignancy of the syndrome [6]. The cutaneous lesions
may occur as long as 25 years before or 37 years after the
internal malignancy and multiple primary carcinomas at
different sites are characteristic of MTS so that up to 9 vis-
ceral cancers in one individual have been reported [10].
Colorectal cancer is the commonest visceral neoplasm to
occur in MTS, and the most frequent initial cancer [3,10].
In common with other forms of HNPCC, colorectal
malignancies in MTS are usually proximal in location and
tend to have a more indolent course than other forms of
colorectal cancer [10]. Fifty-one per cent of MTS patients
develop at least one colorectal cancer, and multiple color-
ectal cancers are common, genitourinary cancers occur in
24% of individuals, mainly transitional cell carcinomas.
Carcinomas of the endometrium, ovary, breast, parotid,
upper GI tract and larynx, and hematological malignan-
cies are also associated with MTS. As in the Lynch II syn-
drome, cancers occur at a relatively young age. Colonic
polyps are found in more than 25% of MTS patients, and
are especially prevalent in patients with colorectal carci-
noma [11].
The genetic disorder in MTS is an autosomal dominant
inherited germline mutation in one of the DNA mismatch
repair genes, MSH1 and MSH2 [8,12]. It is inherited with
a high degree of penetrance and variable expression. The
syndrome occurs in both sexes, with a male to female ratio
of 3:2. Children of an MTS individual, therefore, have a
50% risk of inheriting the cancer predisposition. In fami-
lies where the germline mutation can be identified, those
individuals who have inherited the mutation should be
offered regular screening examinations. In those who can
be demonstrated not to have inherited the germline muta-
tion, cancer surveillance is not necessary [13].
Screening for malignancy at all possible sites is impracti-
cal in MTS given the wide range of associated malignan-
cies, and screening should probably concentrate on the
colorectum, female genital tract and possibly urinary tract.
In some families the occurrence of certain other tumors
would be an indication for other screening modalities, for
example upper GI endoscopy [2].
Cohen et al [10] suggested that a search for internal malig-
nancy should be undertaken in the following: 1) a patient
in whom an MTS-associated sebaceous gland tumor has
been documented, 2) a patient in whom MTS has been
diagnosed and 3) family members of an MTS patient.
They also suggested surveillance program for patients with
MTS or MTS-associated sebaceous gland tumors included
annual clinical examination, CEA, cervical smear, chest
radiography, and urine cytology, colonoscopy or barium
enema every 3–5 years, and for female patients mammog-
raphy 1–2 yearly to age 50 and annually thereafter, and
endometrial biopsy every 3–5 years. Other authors have
suggested that colonoscopy should be more frequent in
view of the high frequency of colonic cancer and its prox-
imal predominance, and advocate annual colonoscopy
from the age of 25 years [3]. Besides, MTS screening may
be laborious but is not universally performed, and a
search for mutations in either MSH1 or MSH2 is expen-
sive and time consuming. One attractive alternative is the
analysis of mismatch repair (MMR) protein expression as
a surrogate for assaying for the respective gene mutations
[12,14].
The indolent course of cancers occurring as part of MTS is
often commented on but has not been shown in any pro-
spective fashion. It has been suggested that because of
their relatively good prognosis and non-aggressive course,
surgical removal of primary or metastatic cancers may be
curative and should be attempted wherever possible
[6,15]. Additionally, the combination of interferon (IFN-
alpha2a) with retinoids (isotretinoin) seems to be of
promise to prevent tumor development in Muir-Torre
syndrome [16]. Besides, oral isotretinoin has been
reported to prevent the development some of the malig-
nancies in this syndrome. A dosage of as 0.8 mg/kg/d may
be effective [3].
In conclusion sebaceous gland tumors are rare and the
diagnosis of such a tumor should suggest the possibility of
Muir-Torre syndrome and prompt a search for associated
malignancies, and for the underlying genetic mutation.
Family members should be monitored to detect early can-
cers and perhaps should be enrolled in chemoprevention
trials. Genetic studies can help identify the inherited
molecular defect that causes the Muir-Torre syndrome.
Competing interests
The author(s) declare that they have no competing inter-
ests.
Authors' contributions
KT: conceived the study, performed the surgical manage-
ment and revised the manuscript for scientific content.
KB: participated in literature search, study design, and
preparation of the manuscript.
KV: participated in literature search, study design and in
the revision of the study and preparation of its final ver-
sion.
TT: participated in study design, literature search and
preparation of the manuscript.
SA: participated in study design and literature search.Page 3 of 4
(page number not for citation purposes)
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Acknowledgements
Patients written consent was obtained for publication of the case report. 
Additionally, the Scientific Council of "G. Papanikolaou" General Regional 
Hospital gave its assent for the publication of data in medical Journal.
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Abstract Background The Muir-Torre syndrome is a rare autosomal dominant condition and is currently considered a subtype of the more common hereditary nonpolyposis colorectal cancer syndrome, in which multiple primary malignancies occur together with sebaceous gland tumors. Case presentation We describe a case of a 62-year-old woman with three primary colorectal tumors, genital tumor, and sebaceous adenomas and present her family history of three generations. Our case represents the first case reported from Greece in the international literature. Conclusion Recognition of the syndrome in patients with sebaceous gland tumors should facilitate early detection of subsequent malignancies if the patient is entered into appropriate screening programs.</p

Tsachalis T

Vasiliadis K

Blouhos K

Tsalis K

Angelopoulos S

Betsis D

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