Adnexal tumours of the skin and familial syndromes.
CUTANEOUS ADNEXAL TUMORS
• Cutaneous adnexal tumors are a large and diverse group of
tumors that are commonly classified according to their state of
appendageal differentiation: eccrine, apocrine, follicular, and
• These tumors generally behave in a benign manner, but
malignant types exist
• Most studies on adnexal neoplasms have taken place in western
countries with Caucasian populations.
• Benign adnexal neoplasms tend to occur in younger patients than
HANDLING SKIN ADNEXAL
• The specimen should be thoroughly sampled after painting its
• The lesion should be serially sectioned at 0.3–0.5-cm intervals
and submitted in its entirety for histological examination.
• Sections including tumoral and grossly uninvolved
surrounding tissue are relevant to evaluate the growth
pattern of the tumour.
• A small/ superficial biopsy may preclude accurate diagnosis of
skin adnexal lesions, and is therefore not advised
• Skin appendages are derived from the ectoderm, and start to
develop early during the embryological life.
• During the fourth week of development, a single-cell-thick
ectoderm and underlying mesoderm begin to proliferate, and
differentiate towards various structures, including skin
• Periodic acid Schiff (PAS) stain, with and without diastase-
cytoplasmic glycogen contents and stromal hyalinised
• Hale’s colloidal iron stain for acid mucin - stromal mucinous
• Prussian blue may be useful in demonstrating iron deposits
within apocrine lesions.
• Monoclonal CEA and EMA - in tumours with ductal
• EMA - in tumours with sebaceous differentiation.
• GCDFP-15 and androgen receptors - in apocrine lesions
• Oestrogen and progesterone receptors - in different sweat
glands lesions and are not considered specific
• Is it a benign or malignant neoplasm?
• Is it a primary adnexal neoplasm or cutaneous metastasis of
• Is it the cutaneous expression of a syndrome assiciated with
an internal malignancy?
Orientation to skin surface Vertically oriented Horizontally oriented
Symmetry and borders Symmetrical with smooth
Cell aggregates Uniform aggregates of
Irregular aggregates of
Necrosis No necrosis en
Necrosis en mass
Cytology and mitoses Monomorphous cells with
variable typical mitoses
Pleomorphic cells with
Stroma Dense fibrotic stroma Infiltration into dermis
and subcutis with scant
PRIMARY CUTANEOUS METASTATIC FROM INTERNAL
Connection to epidermis Deep dermis/subcutaneous tissue
Growth into skin appendages Multifocality
Benign counterpart within the lesion
with entrapped melanocytes
• Skin appendage neoplasms present as papules (‘‘bumps’’) on
the skin that are difficult to distinguish clinically from one
• They can be solitary or multiple.
• Typically multiple when they are associated with an inherited
• Most common presentation - facial papules.
• Clustering on the central facial areas of the nose, nasolabial
folds, upper lip, and forehead.
• Gold standard in diagnosis – histopathological examination of
a skin biopsy
• A 49-year-old man - 10-year history of numerous skin-colored
papules on the mid-face as well as 3 large pedunculated
nodules over the scalp.
• The patient's mother had a history of multiple basal cell
• On examination- three 2-3 cm pink, hairless, pedunculated
nodules were present over the scalp and left preauricular
• A well-circumscribed and
• Predominantly uniform
basaloid cells with peripheral
palisading, arranged in
variably sized nests and
• Dense stroma that contains
• Basaloid- The cells resemble cells from the basal epidermal
layer i.e. have a dark oval nucleus and little cytoplasm
• Benign follicular appendage tumors with differentiation to all
three segments of the hair follicle but in which trichogenesis
is present, incomplete or abortive.
• The epithelial structures - islands of basaloid cells and horn
cysts, which are basically abortive attempts at pilar
• The stromal elements - fibrous stroma that envelopes the
epithelial elements (Rosai, Basam).
• Hair follicles are tubular invaginations of the epidermis, that
develop as downgrowths of the epidermis into the dermis
• The hair follicle -
anatomically divided into an
upper, middle, and lower
• The infundibulum, the
isthmus, and the inferior
THE HAIR FOLLICLE
• The hair follicle consists (from inside out) of the following
• The hair shaft (HS)
• The inner root sheath (IRS)
• The outer root sheath (ORS)
• The perifollicular dermal sheath
Starting from the outside: the cuticle which consists of several layers,
the cortex, which contains the keratin bundles in cell structures that remain roughly rod-
like; and in some cases medulla, a disorganized and open area at the fiber's center.
• The dermal papilla consists
of an egg-shaped
surrounded by ground
• The cells of the hair matrix
have vesicular nuclei and
deeply basophilic cytoplasm
CLUES TO FOLLICULAR
DIFFERENTIATION IN ADNEXAL
• Proliferation of basaloid germinative cells
• peripheral nuclear palisading
• Adjacent papillary mesenchymal cells.
• Matrical shadow (ghost) cells
• Trichilemmal keratinisation
• Tumour is attached to normal follicular structures.
• Differentiation towards many of the normal follicular
elements - generally named accordingly.
• Classifed depending on which part of the hair follicle the
lesion differentiates toward or most closely resembles.
HAIR GERM TUMOURS
• A ‘group of benign cutaneous neoplasms in which hair follicle
development may be partly or completely recapitulated’
• The epithelial component is equivalent to the hair germ.
• The mesenchymal component is equivalent to the dermal
A hair follicle
the hair germ)
forms as a cell
aggregate in the
basal layer of the
• The papilla is a large
structure at the base of the
• Connective tissue and a
TISSUE AND DEEP
SIZE LARGER IN SIZE SMALLER
DIFFERENTIATION HORN CYSTS AND
• Unique histologic feature- papillary-mesenchymal bodies,
which are cup-like proliferations of basaloid cells engulfing
fibroblasts, thus recapitulating papillae of hair follicles
• Bulbar differentiation- emulating the follicular bulb and
• Basal-cell carcinomas - folliculo-
sebaceous-apocrine germ, also
known as the trichoblast..
• Red or pink papules with raised,
rolled borders and pearly, waxy,
or translucent appearance.
• Noduloulcerative BCCs have
indurated edges and central
painless ulcerations that are
covered with crust: “rodent ulcers.
• well-defined, smooth-bordered
basophilic staining islands
• basaloid cells that show
pronounced peripheral palisading
• Retraction artifacts due to
stromal shrinkage in the form of
clefts around the tumor islands
• surrounding stroma with a high
content of mucin
• large homogenous, oval,
elongated nuclei with scant
• high nuclear-to-cytoplasmic
• Rare atypical mitoses.
• Necrotic cells and necrosis
• Autosomal dominant
• Germline mutations in the patched (PTCH) gene on
TUMOURS WITH PREDOMINANT
• Sebaceous tumours
• This pattern should be interpreted in conjunction with other features
such as sebaceous or follicular differentiation, the presence of
cysts/ductal elements or clear cell change, etc
• The hair matrix -
proliferating cells that
generate the hair and the
internal root sheath just
above the dermal papilla.
• Cells in the hair matrix
proliferate and move
becoming keratinised to
produce the hair.
• Melanocytes are present
between the basal cells of
• The matrix cells
differentiate into the
multiple components of the
hair follicle, including the
hair shaft (HS), the inner
root sheath (IRS), and the
outer root sheath (ORS).
CLUES TO MATRIXAL
Basaloid and shadow cells
• Benign tumor arising from hair matrix
• Children and young adults - head, neck or upper extremities
• Associated with Gardner's syndrome, Myotonic dystrophy,
Steinert's disease, Rubinstein-Taybi syndrome, Turner's
syndrome and sarcoidosis.
• Sharply circumscribed with
uniform small dark cells
closely resembling hair
Matrix cell specialization –
• Toward hair cortex with a formation of dense translucent
hyaline substance closely resembling hard keratin
• Towards large squamoid keratinocytes with prominent
keratohyaline granules suggestive of inner sheath cells.
A transition from basaloid to ghost cells
is seen in most areas which may be
abrupt or gradual
The shadow cells are formed due to
keratinization of basaloid cells and
tend to increase in number as the
• Basaloid cells show variable nuclear atypia and mitotic
• asymmetry and poor circumscription, ,markedly sized and
variably shaped basaloid aggregations, and ulceration.
• prominent nucleoli and frequent atypical mitoses and
infiltration into the adjacent tissues.
THE INNER ROOT SHEATH
• The inner root sheath (IRS) surrounds the hair shaft.
• It exists only in the inferior segment of the hair follicle
travelling from the bulb up to the beginning of the isthmus
• The IRS is also made up of three layers: a) the IRS cuticle b)
Huxley’s layer and c) Henley’s layer
OUTER ROOT SHEATH
• Outer root sheath - The outer root sheath (ORS) surrounds
the IRS and consists of multiple layers of epithelial cuboidal
cells containing large quantities of glycogen.
• The thin, clear basement membrane between the inner fibrous
layer of a hair follicle and its outer root sheath.
• Trichilemmoma arises from the outer root sheath of the hair
follicle (mainly of the bulb region).
• Glycogenated clear epithelial cells
with peripheral palisading in
deeper parts ; cells are PAS-
diastase positive ;
• Broad connection with overlying
• epidermal changes resembling
verruca vulgaris present in some
DIAGNOSTIC FEATURE OF
• Evidence of outer root sheath differentiation characterized
• 1. Bland epithelial cells showing peripheral palisading
• 2. Clear cytoplasm
• 3. Prominent intercellular borders
• 4. Thickened and eosinophilic, PAS- positive basement
• Cowden disease (multiple hamartoma syndrome) causes
hamartomatous neoplasms of the skin and mucosa, GI tract,
bones, CNS, eyes, and genitourinary tract.
• Skin is involved in 90-100% of cases, and the thyroid is involved
in 66% of cases.
• Mucocutaneous features of Cowden disease (multiple hamartoma
syndrome) include trichilemmomas, oral mucosal papillomatosis,
acral keratoses, and palmoplantar keratoses.
• The lesions on the
extremities - hyperkeratotic
• Gingival mucosae - multiple
firm whitish papules which
coalesced to give a cobble
stone appearance suggestive
of mucosal fibromas.
• Palmo plantar punctate
keratosis with central
depression and cutaneous
horn on the nape of the neck
• Breast cancer
• Thyroid carcinoma,
especially follicular thyroid
• Macrocephaly (>97
• Lhermitte-Duclos disease
• Endometrial cancer
• Minor criteria
• Other thyroid lesions (eg, adenoma, multinodular
• Mental retardation (intelligence quotient < 75)
• GI hamartomas
• Fibrocystic disease of the breast
• Genitourinary tumors (eg, uterine fibroids, renal cell
carcinoma) or malformations
TUMOURS WITH CLEAR CELL
Clear cell change is indicative of trichilemmal differentiation in
• Poroma and porocarcinoma
Clear cells are glycogen rich and PAS positive
• Clear cell change and adjacent thickened BM is indicative of
trichilemmal differentiation in follicular lesions
• Tumour lobules infiltrating with a pushing border
• Immunocytochemistry reveals positivity for cytokeratin and
negativity for CEA and EMA.
• Trichilemmal (pilar) cysts - common skin lesions on the scalp
of elderly women.
• Proliferating trichilemmal tumour arises from the isthmus
region of the outer root sheath.
• The isthmus is the
shortened segment of the
hair follicle, extending from
the attachment of the
erector pili muscle (bulge
region) into the entrance of
the sebaceous gland duct.
• No keratinisation below the level of isthmus as ORS covered
• However, at the level of the isthmus where the IRS
disintegrates, the ORS keratinizes without forming granules
(trichilemmal keratinization), which is similar to the
keratinization of the hair cortex.
• Well defined lobulated, solid
and cystic mass of
• thick hyalinised basement
• Extension of epithelial
growths into the lumen,
peripheral palisading of
small basaloid cells
• Trichilemmal keratinisation-without granular layer-Pilar
• Trichilemmal keratinization – gain in the bulk and vertical
diameter of the cells, which generally lose their nuclei and
keratinize without the formation of keratohyaline granules.
The infundibulum corresponds to the area from
the opening of the sebaceous duct to the surface
of the skin.
• The infundibular tumors - above the opening of the sebaceous
Dilated pore of Winer and the trichoadenoma
• Isthmic tumors - origin of the sebaceous duct to the level of the
Tumor of the follicular infundibulum) and the pilar sheath
• Hair follicle infundibulum- Keratinous cystic structures
• Rare, benign, well differentiated, slowly growing tumour with
differentiation towards infundibular portion of the hair follicle
which was first described in 1958 by Nikolowski.
• Site: Face & buttocks. Clinically presents as a solitary
NUMEROUS HORN CYST IN THE DERMIS. CYST
LINED BY EOSINOPHILIC CELLS , CONTAIN
• Prominent component of perifollicular mesenchyme, but follicular
elements are also present.
• Trichodiscoma ; Fibrofolliculoma
• Perifollicular fibroma
• Neurofollicular hamartoma
• Spectrum of neoplasms combining a follicular element and the
specialized periadventitial dermis of the upper portion of the
• Fibrofolliculoma-Predominance of epithelial component
• Trichodiscoma- Predominance of connective component ,
• Fibrofolliculoma - very rare benign tumor of the skin that is
derived from the perifollicular sheath.
• Trichodiscoma is a small hamartomatous tumor of the hair
disk with a proliferation of the fibrovascular component of the
• Histologically, they show a mixed proliferation of the external
root sheath of the hair follicles and the surrounding ﬁbrous
• A well-formed central hair
follicle with a dilated
• Anastomosing epithelial
strands that radiate from
the central hair follicle into
the perifollicular fibrotic
• Concentric perifollicular
• Proliferation of cords of
epithelial cells emanating
from the hair follicle
• Horizontally oriented dome
shaped tumour with more
mesenchymal than epithelial
• Prominent stroma of
• Lobules of sebaceous glands
at end of prominent stroma
• Increased dilated capillaries
with perivascular fibrosis
• Multiple fibrofolliculomas- Birt-Hogg-Dube syndrome (BHDS)
that presents with cutaneous fibrofolliculomas,
trichodiscomas, and acrochordons.
• BHDS has an autosomal dominant inheritance with a
mutation on band 17p11.2 that involves a novel BHDS protein
• Multiple (10-100) firm papules of face, neck and/or trunk
• Soft pedonculated lesions (acrochordons /skin tags) skin folds
• More than 10 skin lesions (more with age)
• Minimum 1 lesion confirmed as a Fibrofolliculoma
• Cylindroma is a benign tumour in which apocrine and
trichoepitheliomatous differentiation has been noted
indicating complex hair follicle (folliculo-sebaceous-apocrine)
rather than eccrine differentiation.
• Brooke–Spiegler syndrome (BSS) ,familial cylindromatosis (FC)
and multiple familial trichoepithelioma (MFT) originally
described as distinct entities, share overlapping clinical findings.
• Patients with BSS are predisposed to multiple skin appendage
tumours such as cylindroma, trichoepithelioma, and
• FC, however, is characterised by cylindromas and MFT by
trichoepitheliomas as the only tumour type.
• All three conditions have recently been shown to be allelic.
• Autosomal dominant disease, with high penetrance, and
penetrance increasing with age, and variable expressivity.
• Female predominance
• Predisposition to develop other cutaneous adnexal neoplasms as BCC,
trichoblastomas, follicular cysts, organoid nevi, and malignant transformation
of pre-existing tumors.
• Also patients are at risk for developing tumors of salivary glands, such as
basal-cell adenomas and adenocarcinomas of the parotid glands
Roberto Adrián Retamar, F. Stengel, M. E. Saadi, et, al. Brooke–Spiegler
syndrome – report of four families: treatment with CO 2 laser, International
Journal of Dermatology 2007,46, 583-86.
Putte S. The pathogenesis of familial multiple cylindromas, trichoepitheliomas,
milia, and spiradenomas. Am J Dermatopathol 1995;17: 271-80
• This syndrome is caused by mutations in the tumor
suppressor CYLD gene localized to chromosome 16q
• The most unusual findings – neoplasms with hybrid features,
such as spiradeno-
oepitheliomas, and even the concurrence of all three adnexal
tumors in one lesion
• The most common composite tumor was spiradenocylindroma.
• Sweat glands are simple tubular glands.
• The secretory tubulus and the initial part of the excretory
duct are coiled into a roughly spherical ball at the border
between the dermis and hypodermis.
• The excretory ducts of merocrine sweat glands empty directly
onto the surface of the skin
• The secretory portion is
comprised of larger cells than
• simple cuboidal epithelium,
• duct or conducting portion of
the tubule- two-
layered stratified cuboidal
ECCRINE AND APOCRINE
• Adnexal tumours can differentiate towards the ductal and
or/glandular portion of the eccrine or apocrine glands.
• It is not possible to distinguish on histological ground
between the ductal portion of eccrine and apocrine glands.
CLUES TO SWEAT GLAND AND
• Glandular/duct structures and presence of intracytoplasmic
• True ducts and intracytoplasmic lumina can be highlighted by
their diastase-resistant periodic acid-Schiff (PAS), epithelial
membrane antigen (EMA) and carcinoembryonic antigen
• Apocrine differentiation: Characterized by decapitation
secretion - Ductal changes with apocrine snouting.
(1) intraglandular duct (2) portions, including the transitional segment
between the two segments; (3), intradermal duct; and (4) and (5),
intraepidermal duct (acrosyringium) comprising the lower sweat duct ridge
(4) and the upper spiralled intraepidermal duct (5).
• Originate from the outer cells of the intraepidermal
(acrosyringeal) excretory ducts of eccrine sweat gland.
• The term “poroma” refers to benign adnexal neoplasms with
“poroid” or terminal ductal differentiation.
Three main benign tumours recognised and distinguished
according to their location in relation to the epidermis
(1) poroma involving both epidermis and dermis
(2) hidroacanthoma simplex, also known as intraepidermal
poroma, confined within the epidermis; and
(3) dermal duct tumour, limited to the dermis, with no
• Solid sheets and nodules of basaloid poroid cells
• Small, monomorphous and polyhedral cuboidal, with well-
defined cell membrane.
• Small, centrally located bland nuclei, and a variable amount
of cytoplasm that ranges from scant to ample, eosinophilic to
clear glycogenated PAS positive and diastase sensitive.
• Inconspicuous to prominent CEA-positive small ducts lined by
cuboidal cells, and PAS-positive eosinophilic cuticle material
• Cytoplasmic vacuolation - intracytoplasmic lumen formation -
• Focal sebaceous, pilar and rarely apocrine differentiation may
• Dark epithelial
downgrowths with multiple
attachments to the
• Solid sheets and nodules
Foci of ductal luminal differentiation - small ductal spaces surrounded by
small epithelial cells and covered by eosinophilic lining towards the lumen
were also present
• Secretory portion of eccrine and apocrine glands- Cytokeratin
and CAM 5.2
• Luminal aspect of duct- CEA and EMA
• Clear cell change and rarely display small foci of necrosis en
• Syringomas – A spectrum of benign sporadic tumours that
arise from the straight segment of the intradermal eccrine
• They predominantly affect middle-aged women
• Head and neck region, with a predilection for the eyelids.
• Common in patients with Down syndrome.
Clear cell syringoma are commonly associated with diabetes
• Multiple papules on the lower eyelids and cheeks of adolescent
• Small ducts lined by two layers of cuboidal epithelium
• Ducts have a comma-like tail
• Solid nests and strands of basaloid cells may be present in the
• Some ducts contain eosinophilic material
• Tumour cells CEA in the luminal cells and EMA in the
peripheral cells of the duct.
• ( D/D- CEA is negative in desmoplastic trichoepithelioma).
• Solitary, gray, pink or blue nodule
• It can be painful, often in paroxysms and tend to arise on
head, neck or the upper part of trunk.
• The histogenesis of spiradenomas remains in question, but
many lesions demonstrate apocrine differentiation.
• Large, sharply
nodules (“cannon balls” or
• Intertwining cords, islands,
or sheets in the dermis
surrounded by a fibrous
• Two types of epithelial cells
(1) cells with small, dense, dark nuclei, generally found at the
periphery of the lobules
(2) cells with large pale, vesicular nuclei located in the central
areas of the lobules.
Small rosettes or tubules with lumina sometime containing periodic
acid–Schiff (PAS)-positive and diastase resistant amorphous,
eosinophilic material with scattered lymphocytes
Well-circumscribed dermal tumor with a
grenz zone between the tumour and the
• Variusly shaped tumour islands with small and large lumina
are lined by cuboidal ductal cells or columnar secretory cell
with solid and
cells with ovoid
present at the
the large paler
cells are at the
Two layers of
dark cells and
with PASD +
• Cysts are lined by two layers of cells.
• The inner layer consists of tall columnar
cells with eosinophilic cytoplasm and
showing decapitation secretion.
• The outer layer consists of myoepithelial
cells.. These granules are PAS positive
and diastase resistant.
• Schöpf-Schulz-Passarge - multiple eyelid
apocrine hidrocystomas, palmo-plantar
keratoderma, hypodontia, hypotrichosis
and nail dystrophy.
• Apocrine glands are seen mainly in the axillae, groin, pubic
and perineal regions.
• In contrast with eccrine glands, apocrine glands develop from
an upper bulge in hair follicles
• The histological structure of apocrine sweat glands is similar
to that of merocrine sweat glands
• The lumen of the secretory tubulus is much larger and the
secretory epithelium consists of only one major cell type,
which looks cuboidal or low columnar
The apical portion of glandular cells shows changes specific for
apocrine secretion, namely, the appearance of being decapitated or
• The cytoplasm of apocrine glandular cells might contain iron,
which can be illustrated using Prussian blue stain.
• The luminal cells are characteristically immunoreactant to
gross cystic disease fluid protein 15 (GCDFP-15).
• Glands of Moll-eyelid
• Ceruminous glands-external auditory canal
• as one papule or several
papules in a linear
arrangement, or as a solitary
Raised nodular lesion comprised of multiple cystic, papillary and ductal
invaginations extending into the dermis. Papillary projections are clearly
The epithelium showed double layers of cells consisting of an inner layer of cuboidal cells
and an outer luminal layer of tall columnar cells.
Decapitation secretion was seen in the luminal layer..
•Mononuclear inflammatory infiltrates
consisting of mainly plasma cells in the fibrous
tissue of the papillary projections
•Positive staining in the luminal cells for alcian
blue, colloidal iron, and periodic acid-Schiff
(PAS), which is diastase resistant.
•Positivity for immunohistochemical staining of
gross cystic disease fluid protein 15 (GCDFP-
15; BRST 2), Leu-M1 antigen (CD 15),
lysozymes, carcinoembryonic antigen (CEA),
and epithelial membrane antigen (EMA)
• Almost always located in the vulval or perianal regions.
• Ectopic lesions have been reported on the face, scalp, eyelid,
auditory canal and arm.
• Circumscribed tumour with
papillary and glandular
• There are two types of epithelium - tall columnar cells with
pale eosinophilic cytoplasm and underlying myoepithelial cell
• Prominent apocrine changes are noted in areas.
• The differential diagnosis includes adenocarcinoma.
• PAS positive diastase-
resistant granules are
present in the apices of the
• Sebaceous glands are as a rule simple and branched
• The secretory portion consists of alveoli. Basal cells in the
outermost layer of the alveolus- flattened and mitotically
• Mature sebocytes—cells with a centrally-located, often
scalloped or indented nucleus and multivacuolated cytoplasm
due to the accumulation of lipid secretions
SEBACEOUS LESIONS OF THE
Ectopic Sebaceous Glands:
• Fordyce's spot
Hamartomas and Hyperplasias:
• Folliculosebaceous Cystic Hamartoma
• Nevus Sebaceous of Jadassohn
• Sebaceous Hyperplasia
• Sebaceous Adenoma
• Sebaceous Carcinoma
• The presence of cells with
cytoplasm and starry nuclei
• Ductal structures lined by
crenulated corneocytes - thin
epithelium with a barely
detectable granular zone
• Corneocytes - arranged
compactly, and its luminal
border with distinctive
• Sebaceous neoplasms - potential to arise from any sebaceous
gland in the body.
• They have the greatest predilection for the nose, eyelids, and
other areas with abundant sebaceous glands
• Five or more lobules of
bland, immature sebocytes
that open into a single
• The peripheries of the
lobules have one or two cell
layers of basaloid
• A multilobulated tumour sharply demarcated from the
• Two types of cells are present in the lobules.
• The large mature sebaceous cells (sebocytes) are present at
• Smaller, undifferentiated basaloid cells in the periphery
• Sebaceous adenoma - 50% or more of the cells are sebocytes.
• Ductal structures with holocrine secretion, which may result
in occasional cystic degeneration or formation of intralesional
Basaloid neoplasms with aggregations of basaloid cells
admixed with sebocytes and sebaceous duct-like structures
• Apocrine poroma
• Basal cell carcinoma
MUIR-TORRE SYNDROME (MTS)
• In 1967, Muir and Torre each reported patients with multiple
cutaneous tumors along with visceral malignancies.
• Muir-Torre syndrome (MTS)- sebaceous neoplasms of the skin
and a visceral malignancy (usually gastrointestinal or
• Autosomal dominant pattern of inheritance in 59% of cases
with high degree of penetrance and variable expression.
• MTS - germline mutation in one or more of the DNA
mismatch repair(MMR) genes.
• MTS-associated sebaceous neoplasms reveal mutations in
DNA mismatchrepair (MMR) genes and microsatellite
• Phenotypic variant, the hereditary nonpolyposis colorectal
• Criteria for the diagnosis of MTS-
• At least one sebaceous neoplasm (either sebaceous adenoma,
sebaceous epithelioma, or sebaceous carcinoma; while
sebaceous hyperplasia and nevus sebaceus of Jadassohn are
• At least one visceral cancer.
SEBACEOUS ADENOMA Most characteristic papule or
Benign tumour- yellow papule or nodule
Face, scalp, trunk
SEBACEOUS CARCINOMA Malignant tumour- eyelids
Yellow nodule with ulceration
Metastasis and death
KERATOACANTHOMA Solitary or multiple
Red papule that rapidly grows to become
a skin-coloured, shiny nodule with
telangiectases and a central horny plug
covered by a crust
• exoendophytic, symmetrical lesion characterized by
deep bulbous lobules of keratinizing well
differentiated squamous epithelium with central
keratin filled crater.
• There is marked acanthosis with hyperkeratosis and
little or no parakeratosis.
Cells in the centre of the tumour have a
• There is lipping of edges of normal epidermis that
extends over the central keratinous crater.
• One visceral malignancy or multiple primary malignancies at
• The most common visceral malignancies - colorectal followed
• Colon carcinoma - proximal to the splenic flexure
• Less common malignancies- breast carcinoma, hematological
disorders, endometrial carcinoma, and rarely gastric
• Patients typically present at earlier age with malignancy
SEBACEOUS ADENOMA IN MTS
• Sebaceous adenoma - most characteristic marker of MTS. .
• In the sporadic cases, - head (particularly on the face, the
scalp, and the eyelids),.
• In MTS, lesions on the trunk may be more common.
• The Muir-Torre variant of sebaceous adenoma - more
prominent cystic change, peripheral-disposed basaloid,
germinative-type cells, often with mild nuclear pleomorphism,
distinct nucleoli, and moderate mitotic activity.
• Sebaceous neoplasms with a
pattern probably only occur
in the context of Muir-Torre
Cystic sebaceous neoplasms have been
seen only in patients with Muir-Torre
syndrome (MTS) and have recently been
characterized as marker lesions of MTS
• The occurrence of sebaceous neoplasms in the general
population is rare.
• marker for MTS and should prompt a screening for visceral
• With the exception of sebaceous carcinomas, sebaceous
neoplasms associated with MTS are typically of low malignant
• Recognizing the presence of sebaceous neoplasms can help
identify patients with Muir-Torre syndrome
• Early treatment of an associated occult malignancy may be
Loss of nuclear staining for MLH-1 or MSH-2
is highly suggestive of the syndrome
• Irregular shaped cell masses in which more than 50 percent
cells are undifferentiated, basaloid cells together with
significant aggregates of sebaceous cells and transitional cells.
• The diagnostic criteria for sebaceous carcinomas are
1. silhouette of malignancy (asymmetry, poor circumscription,
and marked variance in size and shape of the neoplastic
2. severe nuclear atypia with frequent mitoses
3. Both seen in the basaloid neoplasms with sebaceous
Immunohistochemical Distinction of Ocular Sebaceous Carcinoma From Basal
Cell and Squamous Cell Carcinoma FREE
John H. Sinard, MD, PhD
Arch Ophthalmol. 1999;117(6):776-783. doi:10.1001/archopht.117.6.77
• EMA immunoperoxidase staining - best supplemental test (in
addition to careful scrutiny of conventional sections) for
confirmation of sebaceous differentiation.
• Positive reaction - EMA labeling of cytoplasm in a coarsely
• EMA, S-100 protein, and carcinoembryonic antigen (CEA)-
differentiation between sebaceous and sweat gland neoplasms
in most instances, the former staining positive for EMA, while
S-100 protein and CEA decorate sweat gland epithelium
• WHO-Skin tumours
• Skin adnexal neoplasms—part 1: An approach to tumours of
the pilosebaceous unit K O Alsaad, N A Obaidat, D Ghazarian
Clin Pathol 2007;60:129–144. doi: 10.1136/jcp.2006.040337
• Skin adnexal neoplasms—part 2: An approach to tumours of
cutaneous sweat glands Nidal A Obaidat, Khaled O Alsaad,
J Clin Pathol 2007;60:145–159. doi: 10.1136/jcp.2006.041608