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SKIN ADNEXAL
TUMOURS AND
FAMILIAL SYNDROMES
NAMRATHA RAVISHANKAR
CUTANEOUS ADNEXAL TUMORS
• Cutaneous adnexal tumors are a large and diverse group of
tumors that are commonly classified a...
EPIDEMIOLOGY
• Epidemiology
• Most studies on adnexal neoplasms have taken place in western
countries with Caucasian popul...
HANDLING SKIN ADNEXAL
TUMOURS
• The specimen should be thoroughly sampled after painting its
resection margins
• The lesio...
• Sections including tumoral and grossly uninvolved
surrounding tissue are relevant to evaluate the growth
pattern of the ...
SKIN APPENDAGES
• Skin appendages are derived from the ectoderm, and start to
develop early during the embryological life....
SPECIAL STAINS
• Periodic acid Schiff (PAS) stain, with and without diastase-
cytoplasmic glycogen contents and stromal hy...
IHC
• Monoclonal CEA and EMA - in tumours with ductal
differentiation.
• EMA - in tumours with sebaceous differentiation.
...
• Is it a benign or malignant neoplasm?
• Is it a primary adnexal neoplasm or cutaneous metastasis of
internal malignancy?...
BENIGN MALIGNANT
Orientation to skin surface Vertically oriented Horizontally oriented
Symmetry and borders Symmetrical wi...
PRIMARY CUTANEOUS METASTATIC FROM INTERNAL
MALIGANCY
Connection to epidermis Deep dermis/subcutaneous tissue
Growth into s...
CLINICAL PRESENTATION
• Skin appendage neoplasms present as papules (‘‘bumps’’) on
the skin that are difficult to distingu...
• Most common presentation - facial papules.
• Clustering on the central facial areas of the nose, nasolabial
folds, upper...
• A 49-year-old man - 10-year history of numerous skin-colored
papules on the mid-face as well as 3 large pedunculated
nod...
• A well-circumscribed and
symmetric lesion
• Predominantly uniform
basaloid cells with peripheral
palisading, arranged in...
• Basaloid- The cells resemble cells from the basal epidermal
layer i.e. have a dark oval nucleus and little cytoplasm
TRICHOEPITHELIOMA
• Benign follicular appendage tumors with differentiation to all
three segments of the hair follicle but...
• Hamartoma & Hyperplasia:
• Benign:
• Carcinoma:
• 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
region.
• The infundibulum, the
isthmus, and t...
THE HAIR FOLLICLE
• The hair follicle consists (from inside out) of the following
concentric layers:
• The hair shaft (HS)...
Starting from the outside: the cuticle which consists of several layers,
the cortex, which contains the keratin bundles in...
• The dermal papilla consists
of an egg-shaped
accumulation of
mesenchymal cells
surrounded by ground
substance
• The cell...
CLUES TO FOLLICULAR
DIFFERENTIATION IN ADNEXAL
TUMOURS
• Proliferation of basaloid germinative cells
• peripheral nuclear ...
• Differentiation towards many of the normal follicular
elements - generally named accordingly.
• Classifed depending on w...
• Hair Germ Differentiation:
Trichoepithelioma
Desmoplastic Trichoepithelioma
Trichofolliculoma
Trichoblastoma
Cutaneous l...
Outer root sheath differentiation:
Trichilemmoma
• Trichilemmal Carcinoma
• Proliferating Trichilemmal Cyst
Matrical diffe...
HAIR GERM TUMOURS
• A ‘group of benign cutaneous neoplasms in which hair follicle
development may be partly or completely ...
A hair follicle
primordium (called
the hair germ)
forms as a cell
aggregate in the
basal layer of the
epidermis during
dev...
• The papilla is a large
structure at the base of the
hair follicle.
• Connective tissue and a
capillary loop
TRICHOGENIC TUMOURS
1. Trichoepithelioma
2. Desmoplastic Trichoepithelioma
3. Trichofolliculoma
4. Trichoblastoma
5. Cutan...
TRICHOEPITHELIOM
A
TRICHOBLASTOMA
LOCATION SUPERFICIAL
WELL
CIRCUMSCRIBED
SUBCUTANEOUS
TISSUE AND DEEP
DERMIS
LESS WELL
CI...
PAPILLARY-MESENCHYMAL
BODIES
• Unique histologic feature- papillary-mesenchymal bodies,
which are cup-like proliferations ...
• Basal-cell carcinomas - folliculo-
sebaceous-apocrine germ, also
known as the trichoblast..
• Red or pink papules with r...
• well-defined, smooth-bordered
basophilic staining islands
• basaloid cells that show
pronounced peripheral palisading
of...
• large homogenous, oval,
elongated nuclei with scant
cytoplasm.
• high nuclear-to-cytoplasmic
ratio,
• Rare atypical mito...
GORLIN SYNDROME
• Autosomal dominant
• Germline mutations in the patched (PTCH) gene on
chromosome 9q22.3
PERIPHERAL PALISADING
• Basaloid follicular hamartoma
• Trichoepitheliomas
• Trichoblastoma
• Trichilemmomas
• Sebaceoma
•...
TUMOURS WITH PREDOMINANT
SMALL/
BASALOID ELEMENTS
• Trichoblastoma/trichoepithelioma
• Pilomatricoma
• Sebaceous tumours
•...
• The hair matrix -
proliferating cells that
generate the hair and the
internal root sheath just
above the dermal papilla....
• Melanocytes are present
between the basal cells of
the matrix.
• The matrix cells
differentiate into the
multiple compon...
CLUES TO MATRIXAL
DIFFERENTIATION
Basaloid and shadow cells
PILOMATRIXOMA
• Benign tumor arising from hair matrix
• Children and young adults - head, neck or upper extremities
• Asso...
• Sharply circumscribed with
uniform small dark cells
closely resembling hair
matrix cells
Matrix cell specialization –
• Toward hair cortex with a formation of dense translucent
hyaline substance closely resembli...
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
neoplasm ages.
PROLIFERATING
PILOMATRIXOMA:
• Basaloid cells show variable nuclear atypia and mitotic
figures
Carcinoma
• asymmetry and p...
PARTIALLY CYSTIC TUMORS- DDX
• Pilomatricoma
• Pilar tumour
• Hidradenoma
• Chondroid syringoma
THE INNER ROOT SHEATH
• The inner root sheath (IRS) surrounds the hair shaft.
• It exists only in the inferior segment of ...
OUTER ROOT SHEATH
• Outer root sheath - The outer root sheath (ORS) surrounds
the IRS and consists of multiple layers of e...
OUTER ROOT SHEATH
DIFFERENTIATION
• Trichilemmoma
• Trichilemmal Carcinoma
• Proliferating Trichilemmal Cyst (Pilar Tumour...
TRICHILEMMOMA
• 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 ;
• Br...
DIAGNOSTIC FEATURE OF
TRICHILEMMOMA:
• Evidence of outer root sheath differentiation characterized
by -
• 1. Bland epithel...
• Cowden disease (multiple hamartoma syndrome) causes
hamartomatous neoplasms of the skin and mucosa, GI tract,
bones, CNS...
• The lesions on the
extremities - hyperkeratotic
verrucous papules
• Gingival mucosae - multiple
firm whitish papules which
coalesced to give a cobble
stone appearance suggestive
of mucosal...
Major criteria
• Breast cancer
• Thyroid carcinoma,
especially follicular thyroid
carcinoma
• Macrocephaly (>97
percentile...
TUMOURS WITH CLEAR CELL
CHANGE
• Trichilemmoma
Clear cell change is indicative of trichilemmal differentiation in
follicul...
TRICHILEMMAL CARCINOMA
• Tumour lobules infiltrating with a pushing border
• Immunocytochemistry reveals positivity for cy...
PROLIFERTING TRICHILEMMAL
(PILAR) CYSTS
• Trichilemmal (pilar) cysts - common skin lesions on the scalp
of elderly women.
...
• The isthmus is the
shortened segment of the
hair follicle, extending from
the attachment of the
erector pili muscle (bul...
• No keratinisation below the level of isthmus as ORS covered
by IRS
• However, at the level of the isthmus where the IRS
...
• Well defined lobulated, solid
and cystic mass of
proliferating epithelium,
• thick hyalinised basement
membrane
• Extension of epithelial
growths into the lumen,
central trichilemmal
keratinisation, and
peripheral palisading of
small ...
• Trichilemmal keratinisation-without granular layer-Pilar
tumour
• Trichilemmal keratinization – gain in the bulk and ver...
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
duct
Dilated pore of Winer and the trichoadenoma
• Isthmic ...
TRICHOADENOMA OF
NIKOLOWSKI
• Rare, benign, well differentiated, slowly growing tumour with
differentiation towards infund...
NUMEROUS HORN CYST IN THE DERMIS. CYST
LINED BY EOSINOPHILIC CELLS , CONTAIN
KERATIN.
FOLLICULAR MESENCHYMAL
DIFFERENTIATION
• Prominent component of perifollicular mesenchyme, but follicular
elements are als...
• Spectrum of neoplasms combining a follicular element and the
specialized periadventitial dermis of the upper portion of ...
• Fibrofolliculoma - very rare benign tumor of the skin that is
derived from the perifollicular sheath.
• Trichodiscoma is...
• A well-formed central hair
follicle with a dilated
infundibulum containing
laminated keratin
• Anastomosing epithelial
s...
• Concentric perifollicular
fibrosis,
• Proliferation of cords of
epithelial cells emanating
from the hair follicle
• Horizontally oriented dome
shaped tumour with more
mesenchymal than epithelial
element
• Prominent stroma of
elliptical ...
• Multiple fibrofolliculomas- Birt-Hogg-Dube syndrome (BHDS)
that presents with cutaneous fibrofolliculomas,
trichodiscoma...
CUTANEOUS SIGNS
• Multiple (10-100) firm papules of face, neck and/or trunk
• Soft pedonculated lesions (acrochordons /ski...
ASSOCIATED INTERNAL DISEASES
Pulmonary manifestations:
• Recurrent spontaneous pneumothorax, lung cysts
• bullous emphysem...
OTHER RARELY ASSOCIATED
DISEASE
• • Medullary thyroid cancer/thyroid adenoma
• • Parotid oncocytoma
• • Multiple lipoma /a...
SCALP NODULE
• The large nodule from the scalp- Dermal tumor
• Large lobulated nests of basaloid cells arranged in a jig-s...
• Two cell type- peripheral
cells are small and
basophilic and central cells
are larger and pale stained.
• Small ductal l...
HYALINE BASEMENT
MEMBRANE
Trichilemmomas
Cylindroma
Steatocystoma
• Cylindroma is a benign tumour in which apocrine and
trichoepitheliomatous differentiation has been noted
indicating comp...
BROOKE–SPIEGLER SYNDROME
(BSS)
• Brooke–Spiegler syndrome (BSS) ,familial cylindromatosis (FC)
and multiple familial trich...
BROOKE–SPIEGLER SYNDROME
(BSS)
• Autosomal dominant disease, with high penetrance, and
penetrance increasing with age, and...
• Predisposition to develop other cutaneous adnexal neoplasms as BCC,
trichoblastomas, follicular cysts, organoid nevi, an...
• 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-
cylindromas,spiradenomas,trichoepitheliom...
• Sweat glands are simple tubular glands.
• The secretory tubulus and the initial part of the excretory
duct are coiled in...
• The secretory portion is
comprised of larger cells than
the duct.
• simple cuboidal epithelium,
along with
interspersed ...
• Hamartoma & Hyperplasia:
• Benign:
• Carcinoma
ECCRINE AND APOCRINE
DIFFERENTIATION
• Adnexal tumours can differentiate towards the ductal and
or/glandular portion of th...
CLUES TO SWEAT GLAND AND
DUCTAL DIFFERENTIATION
• Glandular/duct structures and presence of intracytoplasmic
glandular lum...
(1) intraglandular duct (2) portions, including the transitional segment
between the two segments; (3), intradermal duct; ...
POROMAS
• Originate from the outer cells of the intraepidermal
(acrosyringeal) excretory ducts of eccrine sweat gland.
• T...
POROMA
Three main benign tumours recognised and distinguished
according to their location in relation to the epidermis
(1)...
ECCRINE POROMA
• Solid sheets and nodules of basaloid poroid cells
• Small, monomorphous and polyhedral cuboidal, with wel...
• Inconspicuous to prominent CEA-positive small ducts lined by
cuboidal cells, and PAS-positive eosinophilic cuticle mater...
• Dark epithelial
downgrowths with multiple
attachments to the
epidermis.
• Solid sheets and nodules
Foci of ductal luminal differentiation - small ductal spaces surrounded by
small epithelial cells and covered by eosinophi...
• Secretory portion of eccrine and apocrine glands- Cytokeratin
and CAM 5.2
• Luminal aspect of duct- CEA and EMA
• Clear ...
SYRINGOMA
• Syringomas – A spectrum of benign sporadic tumours that
arise from the straight segment of the intradermal ecc...
SYRINGOMA
• Common in patients with Down syndrome.
Clear cell syringoma are commonly associated with diabetes
mellitus.
• ...
MICROSCOPY
• Small ducts lined by two layers of cuboidal epithelium
• Ducts have a comma-like tail
• Solid nests and stran...
• Immunohistochemistry:
• Tumour cells CEA in the luminal cells and EMA in the
peripheral cells of the duct.
• ( D/D- CEA ...
ECCRINE SPIRADENOMAS
• Solitary, gray, pink or blue nodule
• It can be painful, often in paroxysms and tend to arise on
he...
• Large, sharply
circumscribed, basophilic
nodules (“cannon balls” or
“blue balls”)
• Intertwining cords, islands,
or shee...
• Two types of epithelial cells
(1) cells with small, dense, dark nuclei, generally found at the
periphery of the lobules
...
Small rosettes or tubules with lumina sometime containing periodic
acid–Schiff (PAS)-positive and diastase resistant amorp...
Well-circumscribed dermal tumor with a
grenz zone between the tumour and the
epidermis
• Variusly shaped tumour islands with small and large lumina
are lined by cuboidal ductal cells or columnar secretory cell
HIDRADENO
MAS
POROMA SPIRADENOM
A
SYRINGOMA CYLINDROM
A
Dermal
tumour with
grenz zone
Intraepidermal
and dermal
Well
circu...
HIDROCYSTOMA
• Cysts are lined by two layers of cells.
• The inner layer consists of tall columnar
cells with eosinophilic...
APOCRINE GLANDS
• Apocrine glands are seen mainly in the axillae, groin, pubic
and perineal regions.
• In contrast with ec...
• The histological structure of apocrine sweat glands is similar
to that of merocrine sweat glands
• The lumen of the secr...
The apical portion of glandular cells shows changes specific for
apocrine secretion, namely, the appearance of being decap...
• The cytoplasm of apocrine glandular cells might contain iron,
which can be illustrated using Prussian blue stain.
• The ...
• Hamartoma & Hyperplasia:
• Benign:
• Carcinoma
• as one papule or several
papules in a linear
arrangement, or as a solitary
plaque
Raised nodular lesion comprised of multiple cystic, papillary and ductal
invaginations extending into the dermis. Papillar...
The epithelium showed double layers of cells consisting of an inner layer of cuboidal cells
and an outer luminal layer of ...
•Mononuclear inflammatory infiltrates
consisting of mainly plasma cells in the fibrous
tissue of the papillary projections...
HIDRADENOMA PAPILLIFERUM
• Almost always located in the vulval or perianal regions.
• Ectopic lesions have been reported o...
• Circumscribed tumour with
papillary and glandular
areas.
• There are two types of epithelium - tall columnar cells with
pale eosinophilic cytoplasm and underlying myoepithelial ce...
• PAS positive diastase-
resistant granules are
present in the apices of the
large cells
• Sebaceous glands are as a rule simple and branched
• The secretory portion consists of alveoli. Basal cells in the
outer...
SEBACEOUS LESIONS OF THE
SKIN
Ectopic Sebaceous Glands:
• Fordyce's spot
Hamartomas and Hyperplasias:
• Folliculosebaceous...
• The presence of cells with
coarsely vacuolated
cytoplasm and starry nuclei
(mulberry cells)
• Ductal structures lined by
crenulated corneocytes - thin
cornifying squamous
epithelium with a barely
detectable granula...
• Histochemical
demonstration of
intracellular lipid
• Sebaceous neoplasms - potential to arise from any sebaceous
gland in the body.
• They have the greatest predilection for...
• Five or more lobules of
bland, immature sebocytes
that open into a single
dilated follicular
infundibulum
• The peripher...
• A multilobulated tumour sharply demarcated from the
surrounding tissue.
• Two types of cells are present in the lobules....
• Sebaceous adenoma - 50% or more of the cells are sebocytes.
• Ductal structures with holocrine secretion, which may resu...
Basaloid neoplasms with aggregations of basaloid cells
admixed with sebocytes and sebaceous duct-like structures
• Trichob...
MUIR-TORRE SYNDROME (MTS)
• In 1967, Muir and Torre each reported patients with multiple
cutaneous tumors along with visce...
!!QA
• MTS - germline mutation in one or more of the DNA
mismatch repair(MMR) genes.
• MTS-associated sebaceous neoplasms ...
• Criteria for the diagnosis of MTS-
• At least one sebaceous neoplasm (either sebaceous adenoma,
sebaceous epithelioma, o...
SEBACEOUS ADENOMA Most characteristic papule or
Benign tumour- yellow papule or nodule
Face, scalp, trunk
SEBACEOUS CARCIN...
• exoendophytic, symmetrical lesion characterized by
deep bulbous lobules of keratinizing well
differentiated squamous epi...
• One visceral malignancy or multiple primary malignancies at
different sites.
• The most common visceral malignancies - c...
S
• Less common malignancies- breast carcinoma, hematological
disorders, endometrial carcinoma, and rarely gastric
carcino...
SEBACEOUS ADENOMA IN MTS
• Sebaceous adenoma - most characteristic marker of MTS. .
• In the sporadic cases, - head (parti...
• Sebaceous neoplasms with a
keratoacanthoma-like
pattern probably only occur
in the context of Muir-Torre
syndrome
Cystic sebaceous neoplasms have been
seen only in patients with Muir-Torre
syndrome (MTS) and have recently been
character...
• The occurrence of sebaceous neoplasms in the general
population is rare.
• marker for MTS and should prompt a screening ...
• Recognizing the presence of sebaceous neoplasms can help
identify patients with Muir-Torre syndrome
• Early treatment of...
Loss of nuclear staining for MLH-1 or MSH-2
is highly suggestive of the syndrome
SEBACEOMA
• Sebaceoma
• Irregular shaped cell masses in which more than 50 percent
cells are undifferentiated, basaloid ce...
• The diagnostic criteria for sebaceous carcinomas are
1. silhouette of malignancy (asymmetry, poor circumscription,
and m...
Immunohistochemical Distinction of Ocular Sebaceous Carcinoma From Basal
Cell and Squamous Cell Carcinoma FREE
John H. Sin...
• EMA immunoperoxidase staining - best supplemental test (in
addition to careful scrutiny of conventional sections) for
co...
• EMA, S-100 protein, and carcinoembryonic antigen (CEA)-
differentiation between sebaceous and sweat gland neoplasms
in m...
REFERENCES
• WHO-Skin tumours
• Skin adnexal neoplasms—part 1: An approach to tumours of
the pilosebaceous unit K O Alsaad...
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
Adnexal tumours of the skin and familial syndromes.
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Adnexal tumours of the skin and familial syndromes.

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A histopathological review of the adnexal tumours of the skin and familial syndromes associated with them.

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Adnexal tumours of the skin and familial syndromes.

  1. 1. SKIN ADNEXAL TUMOURS AND FAMILIAL SYNDROMES NAMRATHA RAVISHANKAR
  2. 2. 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 sebaceous. • These tumors generally behave in a benign manner, but malignant types exist
  3. 3. EPIDEMIOLOGY • Epidemiology • Most studies on adnexal neoplasms have taken place in western countries with Caucasian populations. • Benign adnexal neoplasms tend to occur in younger patients than carcinomas do.
  4. 4. HANDLING SKIN ADNEXAL TUMOURS • The specimen should be thoroughly sampled after painting its resection margins • The lesion should be serially sectioned at 0.3–0.5-cm intervals and submitted in its entirety for histological examination.
  5. 5. • 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
  6. 6. SKIN APPENDAGES • 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 appendages.
  7. 7. SPECIAL STAINS • Periodic acid Schiff (PAS) stain, with and without diastase- cytoplasmic glycogen contents and stromal hyalinised basement membrane • Hale’s colloidal iron stain for acid mucin - stromal mucinous degeneration • Prussian blue may be useful in demonstrating iron deposits within apocrine lesions.
  8. 8. IHC • Monoclonal CEA and EMA - in tumours with ductal differentiation. • 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
  9. 9. • Is it a benign or malignant neoplasm? • Is it a primary adnexal neoplasm or cutaneous metastasis of internal malignancy? • Is it the cutaneous expression of a syndrome assiciated with an internal malignancy?
  10. 10. BENIGN MALIGNANT Orientation to skin surface Vertically oriented Horizontally oriented Symmetry and borders Symmetrical with smooth borders Infiltrating borders Cell aggregates Uniform aggregates of cells Irregular aggregates of cells Necrosis No necrosis en mass(except poroma) Necrosis en mass Cytology and mitoses Monomorphous cells with variable typical mitoses Pleomorphic cells with atypical mitoses Stroma Dense fibrotic stroma Infiltration into dermis and subcutis with scant myxoid stroma
  11. 11. PRIMARY CUTANEOUS METASTATIC FROM INTERNAL MALIGANCY Connection to epidermis Deep dermis/subcutaneous tissue Growth into skin appendages Multifocality Benign counterpart within the lesion with entrapped melanocytes Lymphovascular invasion
  12. 12. CLINICAL PRESENTATION • Skin appendage neoplasms present as papules (‘‘bumps’’) on the skin that are difficult to distinguish clinically from one another. • They can be solitary or multiple. • Typically multiple when they are associated with an inherited syndrome.
  13. 13. • 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
  14. 14. • 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 carcinomas (BCC). • On examination- three 2-3 cm pink, hairless, pedunculated nodules were present over the scalp and left preauricular area.
  15. 15. • A well-circumscribed and symmetric lesion • Predominantly uniform basaloid cells with peripheral palisading, arranged in variably sized nests and trabeculae • Dense stroma that contains fibroblasts
  16. 16. • Basaloid- The cells resemble cells from the basal epidermal layer i.e. have a dark oval nucleus and little cytoplasm
  17. 17. TRICHOEPITHELIOMA • 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 differentiation. • The stromal elements - fibrous stroma that envelopes the epithelial elements (Rosai, Basam).
  18. 18. • Hamartoma & Hyperplasia: • Benign: • Carcinoma:
  19. 19. • Hair follicles are tubular invaginations of the epidermis, that develop as downgrowths of the epidermis into the dermis
  20. 20. • The hair follicle - anatomically divided into an upper, middle, and lower region. • The infundibulum, the isthmus, and the inferior segment
  21. 21. THE HAIR FOLLICLE • The hair follicle consists (from inside out) of the following concentric layers: • The hair shaft (HS) • The inner root sheath (IRS) • The outer root sheath (ORS) • The perifollicular dermal sheath
  22. 22. 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.
  23. 23. • The dermal papilla consists of an egg-shaped accumulation of mesenchymal cells surrounded by ground substance • The cells of the hair matrix have vesicular nuclei and deeply basophilic cytoplasm
  24. 24. CLUES TO FOLLICULAR DIFFERENTIATION IN ADNEXAL TUMOURS • 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.
  25. 25. • 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.
  26. 26. • Hair Germ Differentiation: Trichoepithelioma Desmoplastic Trichoepithelioma Trichofolliculoma Trichoblastoma Cutaneous lymphadenoma Infundibular differentiation: Trichoadenoma Dilated Pore of Winer Pilar Sheath Acanthoma Tumour of Follicular Infundibulum
  27. 27. Outer root sheath differentiation: Trichilemmoma • Trichilemmal Carcinoma • Proliferating Trichilemmal Cyst Matrical differentiation: Pilomatrixoma and Pilomatrix Carcinoma Follicular mesenchymal differentiation: • Trichodiscoma ; Fibrofolliculoma • Perifollicular fibroma • Neurofollicular hamartoma
  28. 28. 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 papilla
  29. 29. A hair follicle primordium (called the hair germ) forms as a cell aggregate in the basal layer of the epidermis during development
  30. 30. • The papilla is a large structure at the base of the hair follicle. • Connective tissue and a capillary loop
  31. 31. TRICHOGENIC TUMOURS 1. Trichoepithelioma 2. Desmoplastic Trichoepithelioma 3. Trichofolliculoma 4. Trichoblastoma 5. Cutaneous lymphadenoma
  32. 32. TRICHOEPITHELIOM A TRICHOBLASTOMA LOCATION SUPERFICIAL WELL CIRCUMSCRIBED SUBCUTANEOUS TISSUE AND DEEP DERMIS LESS WELL CIRCUMSCRIBED SIZE LARGER IN SIZE SMALLER DIFFERENTIATION HORN CYSTS AND PAPILLARY MESENCHYMAL BODIES NOT PROMINENT
  33. 33. PAPILLARY-MESENCHYMAL BODIES • Unique histologic feature- papillary-mesenchymal bodies, which are cup-like proliferations of basaloid cells engulfing fibroblasts, thus recapitulating papillae of hair follicles (Basam). • Bulbar differentiation- emulating the follicular bulb and papilla
  34. 34. • 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.
  35. 35. • well-defined, smooth-bordered basophilic staining islands • basaloid cells that show pronounced peripheral palisading of nuclei. • Retraction artifacts due to stromal shrinkage in the form of clefts around the tumor islands • surrounding stroma with a high content of mucin
  36. 36. • large homogenous, oval, elongated nuclei with scant cytoplasm. • high nuclear-to-cytoplasmic ratio, • Rare atypical mitoses. • Necrotic cells and necrosis en masse
  37. 37. GORLIN SYNDROME • Autosomal dominant • Germline mutations in the patched (PTCH) gene on chromosome 9q22.3
  38. 38. PERIPHERAL PALISADING • Basaloid follicular hamartoma • Trichoepitheliomas • Trichoblastoma • Trichilemmomas • Sebaceoma • Pilar tumour
  39. 39. TUMOURS WITH PREDOMINANT SMALL/ BASALOID ELEMENTS • Trichoblastoma/trichoepithelioma • Pilomatricoma • Sebaceous tumours • Poroma • Spiradenoma • Acrospiroma • Cylindroma • 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
  40. 40. • 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 upwards, gradually becoming keratinised to produce the hair.
  41. 41. • Melanocytes are present between the basal cells of the matrix. • 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).
  42. 42. CLUES TO MATRIXAL DIFFERENTIATION Basaloid and shadow cells
  43. 43. PILOMATRIXOMA • 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.
  44. 44. • Sharply circumscribed with uniform small dark cells closely resembling hair matrix cells
  45. 45. 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.
  46. 46. A transition from basaloid to ghost cells is seen in most areas which may be abrupt or gradual
  47. 47. The shadow cells are formed due to keratinization of basaloid cells and tend to increase in number as the neoplasm ages.
  48. 48. PROLIFERATING PILOMATRIXOMA: • Basaloid cells show variable nuclear atypia and mitotic figures Carcinoma • 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.
  49. 49. PARTIALLY CYSTIC TUMORS- DDX • Pilomatricoma • Pilar tumour • Hidradenoma • Chondroid syringoma
  50. 50. 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
  51. 51. 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.
  52. 52. OUTER ROOT SHEATH DIFFERENTIATION • Trichilemmoma • Trichilemmal Carcinoma • Proliferating Trichilemmal Cyst (Pilar Tumour) • Outer root sheath- Clear cells, peripheral palisading and hyaline basement membrane.
  53. 53. TRICHILEMMOMA • Trichilemmoma arises from the outer root sheath of the hair follicle (mainly of the bulb region).
  54. 54. • Glycogenated clear epithelial cells with peripheral palisading in deeper parts ; cells are PAS- diastase positive ; • Broad connection with overlying surface epithelium • epidermal changes resembling verruca vulgaris present in some cases
  55. 55. DIAGNOSTIC FEATURE OF TRICHILEMMOMA: • Evidence of outer root sheath differentiation characterized by - • 1. Bland epithelial cells showing peripheral palisading • 2. Clear cytoplasm • 3. Prominent intercellular borders • 4. Thickened and eosinophilic, PAS- positive basement membrane.
  56. 56. • 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.
  57. 57. • The lesions on the extremities - hyperkeratotic verrucous papules
  58. 58. • 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
  59. 59. Major criteria • Breast cancer • Thyroid carcinoma, especially follicular thyroid carcinoma • Macrocephaly (>97 percentile) • Lhermitte-Duclos disease • Endometrial cancer • Minor criteria • Other thyroid lesions (eg, adenoma, multinodular goiter) • Mental retardation (intelligence quotient < 75) • GI hamartomas • Fibrocystic disease of the breast • Lipomas • Fibromas • Genitourinary tumors (eg, uterine fibroids, renal cell carcinoma) or malformations
  60. 60. TUMOURS WITH CLEAR CELL CHANGE • Trichilemmoma Clear cell change is indicative of trichilemmal differentiation in follicular lesions • Poroma and porocarcinoma Clear cells are glycogen rich and PAS positive • Hidradenoma • Clear cell change and adjacent thickened BM is indicative of trichilemmal differentiation in follicular lesions
  61. 61. TRICHILEMMAL CARCINOMA • Tumour lobules infiltrating with a pushing border • Immunocytochemistry reveals positivity for cytokeratin and negativity for CEA and EMA.
  62. 62. PROLIFERTING TRICHILEMMAL (PILAR) CYSTS • 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.
  63. 63. • 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.
  64. 64. • No keratinisation below the level of isthmus as ORS covered by IRS • 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.
  65. 65. • Well defined lobulated, solid and cystic mass of proliferating epithelium, • thick hyalinised basement membrane
  66. 66. • Extension of epithelial growths into the lumen, central trichilemmal keratinisation, and peripheral palisading of small basaloid cells
  67. 67. • Trichilemmal keratinisation-without granular layer-Pilar tumour • 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.
  68. 68. The infundibulum corresponds to the area from the opening of the sebaceous duct to the surface of the skin.
  69. 69. • The infundibular tumors - above the opening of the sebaceous duct Dilated pore of Winer and the trichoadenoma • Isthmic tumors - origin of the sebaceous duct to the level of the bulge. Tumor of the follicular infundibulum) and the pilar sheath acanthoma. • Hair follicle infundibulum- Keratinous cystic structures
  70. 70. TRICHOADENOMA OF NIKOLOWSKI • 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 papule/nodule.
  71. 71. NUMEROUS HORN CYST IN THE DERMIS. CYST LINED BY EOSINOPHILIC CELLS , CONTAIN KERATIN.
  72. 72. FOLLICULAR MESENCHYMAL DIFFERENTIATION • Prominent component of perifollicular mesenchyme, but follicular elements are also present. • Trichodiscoma ; Fibrofolliculoma • Perifollicular fibroma • Neurofollicular hamartoma
  73. 73. • Spectrum of neoplasms combining a follicular element and the specialized periadventitial dermis of the upper portion of the hair follicle. • Fibrofolliculoma-Predominance of epithelial component • Trichodiscoma- Predominance of connective component , CD34+
  74. 74. • 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 hair • Histologically, they show a mixed proliferation of the external root sheath of the hair follicles and the surrounding fibrous tissue
  75. 75. • A well-formed central hair follicle with a dilated infundibulum containing laminated keratin • Anastomosing epithelial strands that radiate from the central hair follicle into the perifollicular fibrotic stroma
  76. 76. • Concentric perifollicular fibrosis, • Proliferation of cords of epithelial cells emanating from the hair follicle
  77. 77. • Horizontally oriented dome shaped tumour with more mesenchymal than epithelial element • Prominent stroma of elliptical shape • Lobules of sebaceous glands at end of prominent stroma • Increased dilated capillaries with perivascular fibrosis
  78. 78. • 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 called folliculin.
  79. 79. CUTANEOUS SIGNS • 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
  80. 80. ASSOCIATED INTERNAL DISEASES Pulmonary manifestations: • Recurrent spontaneous pneumothorax, lung cysts • bullous emphysema • Risk of spontaneous pneumothorax x 50 • Renal tumors :bilateral, multifocal • Hybrid tumors: chromophobe carcinoma /oncocytoma (67%),Chromophobe Carcinoma (23%),Oncocytoma( 3%) papillary /clear cell carcinoma • Risk of renal tumors x 6,9.
  81. 81. OTHER RARELY ASSOCIATED DISEASE • • Medullary thyroid cancer/thyroid adenoma • • Parotid oncocytoma • • Multiple lipoma /angiolipoma • • Intestinal polyposis • • Neural tissue tumor • • Large connective tissue nevus
  82. 82. SCALP NODULE • The large nodule from the scalp- Dermal tumor • Large lobulated nests of basaloid cells arranged in a jig-saw pattern without attachment to the epidermis
  83. 83. • Two cell type- peripheral cells are small and basophilic and central cells are larger and pale stained. • Small ductal lumina may be present
  84. 84. HYALINE BASEMENT MEMBRANE Trichilemmomas Cylindroma Steatocystoma
  85. 85. • 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.
  86. 86. BROOKE–SPIEGLER SYNDROME (BSS) • 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 spiradenoma. • 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.
  87. 87. BROOKE–SPIEGLER SYNDROME (BSS) • Autosomal dominant disease, with high penetrance, and penetrance increasing with age, and variable expressivity. • Female predominance
  88. 88. • 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
  89. 89. • This syndrome is caused by mutations in the tumor suppressor CYLD gene localized to chromosome 16q
  90. 90. • The most unusual findings – neoplasms with hybrid features, such as spiradeno- cylindromas,spiradenomas,trichoepitheliomas,cylindromatrich oepitheliomas, and even the concurrence of all three adnexal tumors in one lesion • The most common composite tumor was spiradenocylindroma.
  91. 91. • 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
  92. 92. • The secretory portion is comprised of larger cells than the duct. • simple cuboidal epithelium, along with interspersed myoepithelial cells • duct or conducting portion of the tubule- two- layered stratified cuboidal epithelium.
  93. 93. • Hamartoma & Hyperplasia: • Benign: • Carcinoma
  94. 94. ECCRINE AND APOCRINE DIFFERENTIATION • 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.
  95. 95. CLUES TO SWEAT GLAND AND DUCTAL DIFFERENTIATION • Glandular/duct structures and presence of intracytoplasmic glandular lumina. • True ducts and intracytoplasmic lumina can be highlighted by their diastase-resistant periodic acid-Schiff (PAS), epithelial membrane antigen (EMA) and carcinoembryonic antigen positivity. . • Apocrine differentiation: Characterized by decapitation secretion - Ductal changes with apocrine snouting.
  96. 96. (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).
  97. 97. POROMAS • 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.
  98. 98. POROMA 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 epidermal attachment
  99. 99. ECCRINE POROMA • 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.
  100. 100. • 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 be identified.
  101. 101. • Dark epithelial downgrowths with multiple attachments to the epidermis. • Solid sheets and nodules
  102. 102. Foci of ductal luminal differentiation - small ductal spaces surrounded by small epithelial cells and covered by eosinophilic lining towards the lumen were also present
  103. 103. • 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 masse.
  104. 104. SYRINGOMA • Syringomas – A spectrum of benign sporadic tumours that arise from the straight segment of the intradermal eccrine sweat duct. • They predominantly affect middle-aged women • Head and neck region, with a predilection for the eyelids.
  105. 105. SYRINGOMA • Common in patients with Down syndrome. Clear cell syringoma are commonly associated with diabetes mellitus. • Multiple papules on the lower eyelids and cheeks of adolescent females
  106. 106. MICROSCOPY • 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 dermis • Some ducts contain eosinophilic material
  107. 107. • Immunohistochemistry: • Tumour cells CEA in the luminal cells and EMA in the peripheral cells of the duct. • ( D/D- CEA is negative in desmoplastic trichoepithelioma).
  108. 108. ECCRINE SPIRADENOMAS • 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.
  109. 109. • Large, sharply circumscribed, basophilic nodules (“cannon balls” or “blue balls”) • Intertwining cords, islands, or sheets in the dermis surrounded by a fibrous capsule
  110. 110. • 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.
  111. 111. Small rosettes or tubules with lumina sometime containing periodic acid–Schiff (PAS)-positive and diastase resistant amorphous, eosinophilic material with scattered lymphocytes
  112. 112. Well-circumscribed dermal tumor with a grenz zone between the tumour and the epidermis
  113. 113. • Variusly shaped tumour islands with small and large lumina are lined by cuboidal ductal cells or columnar secretory cell
  114. 114. HIDRADENO MAS POROMA SPIRADENOM A SYRINGOMA CYLINDROM A Dermal tumour with grenz zone Intraepidermal and dermal Well circumscribed Dermal tumour Dermal tumour Dermal tumor with no attachment to epidermis Variably shaped islands with solid and cystic areas Cords, nests and islands Circumcribed lobules with basement membrane Ducts, solid nests and strands Jigsaw puzzle pattern Polyhedral and round cells Monomorphic cells with ovoid nuclei Small cells with dark nuclei are present at the periphery and the large paler cells are at the centre Two layers of cuboidal epithelium Peripheral dark cells and central pale cells Ductal differentiation and intracytoplasm ic lumina Narrow ductal lumina Small lumina with PASD + material Ducts with comma like tails and eosinophilic material Small ductal lumina with hyaline droplets
  115. 115. HIDROCYSTOMA • 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.
  116. 116. APOCRINE GLANDS • 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
  117. 117. • 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
  118. 118. The apical portion of glandular cells shows changes specific for apocrine secretion, namely, the appearance of being decapitated or pinched off
  119. 119. • 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
  120. 120. • Hamartoma & Hyperplasia: • Benign: • Carcinoma
  121. 121. • as one papule or several papules in a linear arrangement, or as a solitary plaque
  122. 122. Raised nodular lesion comprised of multiple cystic, papillary and ductal invaginations extending into the dermis. Papillary projections are clearly
  123. 123. 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..
  124. 124. •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)
  125. 125. HIDRADENOMA PAPILLIFERUM • Almost always located in the vulval or perianal regions. • Ectopic lesions have been reported on the face, scalp, eyelid, auditory canal and arm.
  126. 126. • Circumscribed tumour with papillary and glandular areas.
  127. 127. • There are two types of epithelium - tall columnar cells with pale eosinophilic cytoplasm and underlying myoepithelial cell layer. • Prominent apocrine changes are noted in areas. • The differential diagnosis includes adenocarcinoma.
  128. 128. • PAS positive diastase- resistant granules are present in the apices of the large cells
  129. 129. • 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 active. • Mature sebocytes—cells with a centrally-located, often scalloped or indented nucleus and multivacuolated cytoplasm due to the accumulation of lipid secretions
  130. 130. SEBACEOUS LESIONS OF THE SKIN Ectopic Sebaceous Glands: • Fordyce's spot Hamartomas and Hyperplasias: • Folliculosebaceous Cystic Hamartoma • Steatocystoma • Nevus Sebaceous of Jadassohn • Sebaceous Hyperplasia Benign: • Sebaceous Adenoma • Sebaceoma Malignant: • Sebaceous Carcinoma
  131. 131. • The presence of cells with coarsely vacuolated cytoplasm and starry nuclei (mulberry cells)
  132. 132. • Ductal structures lined by crenulated corneocytes - thin cornifying squamous epithelium with a barely detectable granular zone • Corneocytes - arranged compactly, and its luminal border with distinctive crenulations.
  133. 133. • Histochemical demonstration of intracellular lipid
  134. 134. • 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
  135. 135. • Five or more lobules of bland, immature sebocytes that open into a single dilated follicular infundibulum • The peripheries of the lobules have one or two cell layers of basaloid germinative cells.
  136. 136. • A multilobulated tumour sharply demarcated from the surrounding tissue. • Two types of cells are present in the lobules. • The large mature sebaceous cells (sebocytes) are present at the centre. • Smaller, undifferentiated basaloid cells in the periphery
  137. 137. • 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 cysts
  138. 138. Basaloid neoplasms with aggregations of basaloid cells admixed with sebocytes and sebaceous duct-like structures • Trichoblastoma • Apocrine poroma • Basal cell carcinoma
  139. 139. 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 genitourinary carcinomas). • Autosomal dominant pattern of inheritance in 59% of cases with high degree of penetrance and variable expression.
  140. 140. !!QA • 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 instability. • Phenotypic variant, the hereditary nonpolyposis colorectal cancer (HNPCC)
  141. 141. • 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 generally excluded) • At least one visceral cancer.
  142. 142. 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
  143. 143. • 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 "glassy" appearance. • There is lipping of edges of normal epidermis that extends over the central keratinous crater.
  144. 144. • One visceral malignancy or multiple primary malignancies at different sites. • The most common visceral malignancies - colorectal followed by genitourinary. • Colon carcinoma - proximal to the splenic flexure
  145. 145. S • Less common malignancies- breast carcinoma, hematological disorders, endometrial carcinoma, and rarely gastric carcinoma • Patients typically present at earlier age with malignancy
  146. 146. 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.
  147. 147. • Sebaceous neoplasms with a keratoacanthoma-like pattern probably only occur in the context of Muir-Torre syndrome
  148. 148. Cystic sebaceous neoplasms have been seen only in patients with Muir-Torre syndrome (MTS) and have recently been characterized as marker lesions of MTS
  149. 149. • The occurrence of sebaceous neoplasms in the general population is rare. • marker for MTS and should prompt a screening for visceral malignancy • With the exception of sebaceous carcinomas, sebaceous neoplasms associated with MTS are typically of low malignant potential.
  150. 150. • Recognizing the presence of sebaceous neoplasms can help identify patients with Muir-Torre syndrome • Early treatment of an associated occult malignancy may be started.
  151. 151. Loss of nuclear staining for MLH-1 or MSH-2 is highly suggestive of the syndrome
  152. 152. SEBACEOMA • Sebaceoma • 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.
  153. 153. • The diagnostic criteria for sebaceous carcinomas are 1. silhouette of malignancy (asymmetry, poor circumscription, and marked variance in size and shape of the neoplastic aggregations) 2. severe nuclear atypia with frequent mitoses 3. Both seen in the basaloid neoplasms with sebaceous differentiation.
  154. 154. 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
  155. 155. • 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 vacuolated pattern.
  156. 156. • 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
  157. 157. REFERENCES • 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, Danny Ghazarian J Clin Pathol 2007;60:145–159. doi: 10.1136/jcp.2006.041608

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