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SKIN ADNEXAL TUMORS
INTRODUCTION
• Skin adnexal tumours can be benign or malignant lesions with differentiation similar to
one or more types pf adnexal epithelium found in normal skin
• Skin appendages are derived from the ectoderm
• These lesions are divided into three major groups on the basis of types of adnexal
structures :
• Hair follicles
• Sebaceous glands
• Apocrine / eccrine glands
Normal
histology of skin
appendages
• Normal skin adnexal structures
include hair follicles with
associated apocrine and
sebaceous glands
• The eccrine glands attaches
directly to the epidermis
PILOSEBACEOUS
UNIT
• Hair follicle is tubular invagination from the
epidermis , responsible for formation if hair a
highly modified keratinised structure
• Highly vascular connective tissue papillae
enclosed by bulbous expansion are located in
the reticular dermis or in the superficial
subcutaneous fatty tissue and from lower
portion of the hair follicle
• the hair shaft consists of an innermost
medulla surrounded by a broad , highly
keratinised cortical layer and an outermost
thin layer of overlapping keratin
SEBACEOUS GLANDS
SWEAT GLANDS
• There are two types of sweat glands
• Apocrine sweat glands
• Eccrine sweat glands
ECCRINE SW
GLAND
APOCRINE SWEAT GLANDS
• Secretion is due to separation of the apical cap which was formed during the
maturation of gland
WHO
CLASSIFICATION
SEBACEOUS TUMORS
Sebaceous proliferations are usually easy to recognize because of the
vacuolated bubbly , mature sebocytes that are present in varying
proportions in the most sebaceous lesions
Mature sebocytes will possess 3 criteria:
• Sharply marginated round cytoplasmic vacuoles
• Vacuoles that are optically clear ( white)
• Vacuoles that scallop / indent into nuclear membrane
Sebaceous hyperplasia
Clinical Features
• Older individuals
• Face, mammary areola, genital skin
• Yellowish to tan papules, often umbilicated
• Rare linear or giant forms
Histopathologic Features
• Single follicular canal opens to umbilicated epidermal surface
• Four or more sebaceous lobules attached to central infundibulum of
sebaceous follicle
• Fully mature sebaceous lobules composed of sebocytes with compact
nuclei and abundant multivacuolated clear cytoplasm
Sebaceous hyperplasia: the sebaceous lobules
drain through short ductules into the central duct.
.
Sebaceoma
• Sebacoma presents as a yellow-to-orange or flesh-colored papule, nodule
or tumor measuring approximately 1–3 cm in diameter
• These tumors are usually solitary , flesh colored to yellowish papulonodules
on the face or scalp
• They may be multiple if they are associated with muir torre syndrome
• Histopathology :
• There are multiple nests of basaloid cells with random mixture of sebaceous
cells wither solitary or in clusters
• The tumor is centred on the upper and mid dermis but some nests may be
continuous with the basal layer of the epidermis
• The small basaloid cells of the tumor outnumber the mature sebaceous
component
• There are scattered mitoses but the tumor lacks the atypia of sebaceous
carcinoma
Sebaceoma: there is a multinodular
dermal tumor showing multiple
points of origin/contact with the
epidermis.
Sebaceoma: (A) the tumor consists of a random admixture of basaloid cells and mature sebocytes; (B) in this field,
there are two mitoses. There is no significant atypia.
• Differential diagnosis :
• Sebaceoma can be distinguished from sebaceous adenoma in which a lobular architecture with distinct
and regular maturation (mimicking the normal sebaceous gland) is typically present.
• Sebaceous adenoma generally presents as a solitary nodular lesion in the superficial dermis, frequently
replacing the overlying epidermis in whole or in part.
• It should be noted, however, that focal sebaceous adenoma-like features may sometimes be seen in a
background of more typical sebaceoma
Sebaceous adenoma
• Clinical Features
• Patient often older than 50 years of age
• Head and neck, especially face
• Yellowish nodule
• Usually <1 cm but can be :l:S cm
• Association with Muir-Torre syndrome
(sebaceous neoplasms, squamous cell
carcinomas, and visceral carcinomas
[laryngeal and gastrointestinal)
• Histopathologic Features
• Classical type
• Well-defined enlarged sebaceous lobules
• Frequent attachment to epidermis with epidermal thinning
• Fully mature sebocytes
• Lobules may contain ductlike structures
• Variant type (Muir-Torre)
• Sharp demarcation of lobules may be lacking Lobules show admixture of
peripherally located basaloid epithelium (50%) centrally mature sebocytes
• Basaloid epithelium may show slight nuclear pleomorphism,
distinct nucleoli, and occasional mitoses
• Differential Diagnosis
• Sebaceous hyperplasia
• Sebaceoma
• Basal cell carcinoma with sebaceous differentiation
Sebaceous adenoma: (A) this example has been shelled out. Note the circumscribed border; (B) there is a
peripheral layer of basophilic germinative cells and inner sebaceous cells with bubbly cytoplasm and
crenated nuclei.
Malignant sebaceous tumors
• Clinical Features
• Middle-aged and elderly patients (mean age, 62 years)
• Predilection for Asians
• Ocular (upper eyelids) more often than extraocular sites (head and neck more often than
trunk, genitalia, extremities)
• Nontender mass
• Histopathologic Features
• Bowenoid or pagetoid pattern of atypical epithelial cells within epidermis or
conjunctiva ,epithelium, or both
• Lobular dermal aggregates of variably atypical polyhedral cells
• Central necrosis ("comedo" pattern) common
• Well-differentiated tumors: cells with abundant multivacuolated cytoplasm,
vesicular nuclei, and discernible nucleoli
• Poorly differentiated tumors: nondescript cells with high
nucleocytoplasmic ratios, prominent nuclear pleomorphism,
prominent nucleoli, prominent mitotic activity
• Basaloid SC: small cells with scanty cytoplasm, peripheral
palisading, nuclear anaplasia
• Squamoid SC: prominent squamous metaplasia with keratin
pearls
• Sarcomatoid SC: spindle cell features
• lmmunohistochemistry
• EMA+, Androgen receptor+, Adipophilin+,
• Factor XI Ila (clone AC-1A1 )+
• BerEp4-, CEA-, pan CK+, CK7+, p40+, p63+,
• CD10+, KIT+, Melan-A
• Differential Diagnosis
• Sebaceous adenoma
• Sebaceoma
• Clear cell squamous cell carcinoma
• Clear cell basal cell carcinoma
• Balloon cell melanoma
• Trichilemmal carcinoma
• Merkel cell carcinoma
• Sebaceous carcinoma. (A} Small, well· differentiated
tumor. Note lobular architecture with discrete tumor
lobules separated by a nondesmoplastic
fibrousstroma.
• {B) A large proportion of clear cells are observed in
this well-differentiated variant
Sebaceous neoplasms and muir torre
syndrome
• Some sebaceous adenomas, sebaceomas, and sebaceous carcinomas are associated with
MTS.
• Sebaceous hyperplasia has no association with this syndrome, nor does nevus sebaceus.
• Muir-Torre syndrome is a variant of hereditary nonpolyposis colorectal cancer syndrome
(also referred to as Lynch syndrome).
• It is the result of a germline mutation in one of several DNA mismatch repair (MMR)
genes, most notably MLH1, MSH2, MSH6, and PMS2.
• Unlike classic Lynch syndrome, where MLH1 mutations predominate, MSH2 is the most
common germline-mutated MTS-associated gene.
• A second hit to the other allele of the mutated mismatch repair gene results in
microsatellite instability and may lead to subsequent development of cancer.
• MMR protein expression in sebaceous lesions can be assessed by IHC.
• Like in classic Lynch syndrome, because MMR proteins are paired in the cell, loss of one
may affect the presence of another.
• MLH1 is paired with PMS2; as the dominant partner, if MLH1 is lost, PMS2 is also lost
(but not vice versa).
• Similarly, MSH2 and MSH6 are partners; as the dominant partner, if MSH2 is lost, then
MSH6 is also lost (but not vice versa).
• The combination of positive and negative staining should yield enough information to
identify the putative defective gene
• solid sheets of basaloid cells in some lobules or an intermingling of these cells and
sebaceous cells without any orderly maturation.
• Sometimes the tumors resemble a basal cell carcinoma but with focal sebaceous
differentiation.
• Mucinous and cystic areas may be present
• Cystic components are important component of this syndrome
• All sebaceous tumors should be screened for the presence of MSH-2, MSH-6, MLH-1,
and PMS-2, the respective gene products of MSH2, MSH6, MLH1, and PMS2
• The diagnosis of Muir–Torre syndrome is made when nuclear staining for the particular
gene product is absent in the tumors
• The cells express epithelial membrane antigen and nuclear androgen receptor
Immunohistochemistry of sebaceous tumors
Immunohistochemistry
Target action
Function
EMA Strong positivity and highlights vacuoles of more mature sebocytes.
Recognizing vacuolated patterns on EMA staining is the most
important feature
Adipophilin Strongly highlights cytoplasmic vacuoles in more mature sebocytes
P63 and p40 P63 and p40 are expressed in the basaloid germinative cells of
normal sebaceous gland
CK7 Most sebaceous tumours show CK 7 positivity
CEA Sebaceous tumours are negative for CEA
Ber-EP4 Negative in sebacoma positive in basal cell carcinoma
FACTOR XIII a ( iclone AC-1A1) Nuclear staining of normal and neoplastic sebocytes
USEFUL HISTOLOGICAL FEATURES FOR DISTINGUISHING BETWEEN SEBACOMA AMD BASAL CELL CARCINOMA WITH SEBACEOUS
DIFFERENTIATION
FEATURES SEBACOMA BCC WITH SEBACEOUS DIFFERENTIATION
OVERALL MORPHOLOGY SIMILAR TO SEBACEOUS ADENOMA BUT WITH MORE
BASALOID COMPONENT
Similar to classical BCC,
but with a component of
sebaceous
differentiation
Main components Aggregates of basaloid
germinative cells
admixed with single units
or clusters of mature
vacuolated sebocytes
Aggregate of follicular
germinative basaloid
cells
Architectural pattern Benign malignant
Cytological features Monomorphous basaloid
cells, with small oval
nuclei and non-prominent
nucleoli
Pleomorphic basaloid
cells, with slightly
elongated nuclei
Mitotic activity Mild/absent Brisk
Sebaceous differentiation Prominent Focal and associated with apocrine differentiation in
many cases
Peripheral palisading
Artefactual clefting
Absent
Absent
Present
Present
Other associated
features
Sebaceous duct-like
structures, rare squamous
differentiation, and
dense eosinophilic
dermal sclerosis
Sebaceous duct-like
structures, individual cell
necrosis, keratinization
and mucinous stroma
Tumors with focal sebaceous differentiation
• These tumors show sebaceous differentiation or sebaceous glands can be seen in the
following :
• Basal cell carcinoma
• Squamous cell carcinoma
• Trichoblastoma
• Seborrheic keratosis
• Dermatofibroma
• Reticulated acanthoma
Trichoblastoma with sebaceous differentiation It is characterised by sebocytes and sebaceous
duct like structures within basaloid
aggregations of a large nodular type of
trichoblastoma
seborrhic keratosis with sebaceous
differentiation
Areas of seborrheic keratosis with admixed
sebocytes occurring in clusters or as a single
cells
Microcysts with variable resemblance to
sebaceous ducts are usually present
They are much smaller than horn cysts of
seborrheic keratosis
Verruca vulgaris with sebaceous differentiation
:
Rare entity
Sometimes focal apocrine differentiation may
also be present
Reticulated acanthoma with sebaceous differentiation have been called as superficial epithelioma
with sebaceous differentiation
Apocrine poroma with sebaceous resembles eccrine poroma
Sweat gland tumors
• Sweat gland tumors have been divided into apocrine and eccrine
• The distinction between apocrine and eccrine is difficult because the ducts of each gland
type are identical
• Fulton et al had arranged sweat gland tumors into 6 groups based on common
histologic patterns
PATTERN 1 : DERMAL CYST WITH DOUBLE
CUBOIDAL / COLUMNAR LINING
HIDROCYSTOMA CYSTADENOMA
HIDROCYSTOMA
• They are simplest benign sweat gland tumors
• They present as small translucent papules on the upper
cheek near the eye
• The cysts are unilocular and are lined by two layers of
cuboidal epithelium
• CK 7 , 8 and 19 are present in these tumors , on the
basis of this they were regarded as being of eccrine
origin
The cysts are lined by two layers of cells:
(1) an inner lining of large columnar cells with eosinophilic cytoplasm often showing luminal
decapitation secretion
(2) an outer flattened layer of myoepithelial cells.
CYSTADENOMA :
• When the lining of hidrocystoma becomes thicker or more
complex
• Then these terms are called as cystadenoma
PATTERN 2 : SOLID PINK /CLEAR
/SQUAMOID PROLIFERATION IN EPIDERMIS
AND / OR DERMIS +/- CYSTIC CHANGE
• ACROSPIROMAS ( HIDROACANTHOMA SIMPLEX , POROMA ,
DERMAL DUCT TUMOR , HIDRADENOMA ) AND THEIR
MALIGNANT COUNTER PARTS
Hidroacanthoma simplex
• Hidroacanthoma simplex (intraepidermal eccrine poroma) is a solitary
plaque or nodular lesion found particularly on the extremities and the
trunk
• It arises throughout adult life, and there is an equal sex incidence.
Clinically, it resembles a seborrheic keratosis or basal cell carcinoma.
• Histopathology
• Hidroacanthoma simplex is composed of well-circumscribed nests of
cuboidal to oval basaloid cells within the epidermis, resembling those
seen in eccrine poroma
POROMA
• Poroma is a benign adnexal tumor with differentiation towards the intradermal
portion of the sweat apparatus
• It is divided into :
• Eccrine poroma
• Dermal eccrine poroma
• Hidracanthoma simplex ( intraepidermalporoma)
• Syringoacanthoma
• Syringofibroadenoma
• These lesions contains two or three histologically components
• Hidroacanthoma simplex
• Eccrine poroma
• Dermal duct tumor
Eccrine poroma
• Clinical presentation :
• Solitary , pink or red exophytic nodule
• Plantar or palmar skin on the lower extremities and hands
• Age group : middle aged or elderly
• Histopathology
• Eccrine poroma is a circumscribed tumor composed of cords
and broad columns of uniform basaloid cells extending into the
dermis from the undersurface of the epidermis
• Cells are PAS positive and diastase sensitive
DERMAL DUCT TUMOR
• Tumor composed of basaloid cells , like a eccrine poroma but located
in the dermis
• Clinical :
• Papule, plaque or nodule in the lower limbs or head and neck region
• Histopathology :
• Tumor is composed of islands of basaloid tumor cells within the
dermis
• Duck like structure are prominent in many of the nests and tumor
may connect with a normal appearing eccrine duct
• Epidermal connection is often found in multiple sections examined
• Cells are PAS positive , sometimes melanin pigments are found
• Clear cell variant :
• Multiple solid aggregates of clear cells involving the dermis
• Ductal structures are also present
• Differential diagnosis :
• Porocarcinoma : infiltrative growth and areas of spontaneous
necrosis is seen
HIDRADENOMA ( ACROSPIROMA)
• There are two variants of hidradenoma
• Apocrine hidradenoma
• Eccrine hidradenoma ( poroid hidradenoma )
• Apocrine hidradenoma is composed of clear , polygonal and
mucinous cells
• Eccrine hidradenoma consist of poroid and cuticular cells
Apocrine hidradenoma
• Clinical presentation :
• Solitary nodules 2 or 3 cm in diameter
• Predominantly seen in females
• There is no site predilection
• They may be associated with t (11;19) has been reported in
breast parenchyma
• HISTOPATHOLOGY :
• Hidradenomas are circumscribed non encapsulated multilobular
tumors centred on the dermis and sometimes extends into subcutis
• Epidermal connections are present
• Tumor cells may be round , fusiform or polygonal in shape are
biphasic in cytoplasmic architecture
• Some cells show clear cell change
• Duct like structures are often present in the tumor .
• Some resemble eccrine or apocrine ducts
• The stroma between lobules varies from thin , delicate , vascularized
collagen
• Immunohistochemistry :
• Low molecular weight cytokeratin (CAM 5.2)
• Some also express CEA and EMA
• Smooth muscle actin and S100 protein were coexpressed
Hidradenoma ( poroid hidradenoma )
• Eccrine hidradenoma ( poroid hidradenoma ) is circumscribed ,
non encapsulated dermal tumor composed of poroid and
cuticular cells
• Ductal structures may form , particularly within the zones of
cuticular cells
• It lacks polygonal , clear and mucinous cells of apocrine variant
Hidradenoma shows clear cells . The nuclei are smaller than in eosinophilic cells
Poroid hidradenoma. This lesion
has the cytological characteristics
of a poroma, and it lacks
polygonal, clear, or mucinous
cells. Ductal structures ca be
identified within the tumor
MALIGNANT ACROSPIROMA
• These tumors posses architectural similarities to their benign
counterpart
• They show cytologic atypia , brisk or atypical mitotic activity and
/or infiltrative growth pattern
• Eg : porocarcinoma , hidradenocarcinoma
POROCARCINOMA
• CLINICAL FEATURES :
• Older individuals , often > 60 years
• Lower extremities , head and neck , upper extremities , trunk
• Verrucous papule or nodule , may ulcerate
• High rate of recurrence
• Regional lymph node metastases
• Tendency to multiple multiple epidermotropic metastases
• Histologic features :
• Features of poroma
• Infiltrative features
• Often desmoplastic stroma is seen
• Tumor necrosis
• Cytologic atypia and mitoses is seen
• Extensive clear cell change is seen
• Differential diagnosis :
• Eccrine poroma
• Squamous cell carcinoma
• Hidradenocarcinoma
• Trichilemmal carcinoma
• Amelanotic melanoma
Porocarcinoma : lobular
aggregates of atypical
cuboidal tumor cells extend
from epidermis into dermis
Scant solitary poroid carcinomatous
tumor nests within the epidermis are
associated with dermal invasion by tuor
aggregates with conspicuous cytologic
HIDRADENOCARCINOMA
• Formerly named as malignant acrospiroma
• Malignant counterpart of hidradenoma
• Clinical features :
• Nodules involving head and neck area , the extremities
• Tumor may ulcerate
• Associated with frequent metastases
• Histopathologic features :
• Dermal based tumid composed of lobules of polygonal
eosinophilic or clear cells
• Occasional basaloid and squamous foci
• Ductal structures
• Infiltrative growth pattern
• Three morphologic variants :
• Polypoid configuration of tumor
• Sclerosing variant with marked desmoplasia
• Comedo variant showing central necrosis within lobular
epithelial aggregates
• Differential diagnosis :
• Porocarcinoma
• Squamous cell carcinoma
• Sebaceous carcinoma
Large lobular dermal tumor with superficial cystic spaces
and comprised of irregular nests of basaloid tumor cells
Large lobular aggregates of tumor
cells exhibit variable clear cell
change and focal necrosis
PATTERN 3 : BLUE BASALOID
PROLIFERATION IN DERMIS
• SPIRADENOMA
• CYLINDROMA
CYLINDROMA
• Clinical features :
• Head and neck especially scalp
• Multiple tumors ( turban tumors)
• Autosomal dominant
• Association with spiradenomas and trichoepitheliomas
• Histopathologic features :
• Mosaic or jigsaw puzzle patter of tumor islands
• Tumor aggregates delimited by basement membrane material
that also results in hyaline droplets within aggregates
• Basaloid tumor aggregates with 2 cellular populations
• Outer layer composed of small , round cells with scant cytoplasm
• Inner layer comprised of larger polygonal cells with more abundant
cytoplasm
• Irregular pattern at periphery of tumor
• Occasional mitotic figures
• Differential diagnosis :
• Basal cell carcinoma
• Spiradenoma
SPIRADENOMA
• CLINICAL FEATURES
Trunk , ventral surfaces
Skin colored or bluish white cystic or spongelike consisitency
Painful or tender
Histopathology :
Rounded tumor lobules often large and few in number
No epidermal connection or jigsaw puzzle pattern
Tumor lobules delimited by basement membrane material and contain hyaline
droplets
Smaller outer cells
Large inner polygonal cells
May contain small ductular structures
• Differential diagnosis
• Basal cell carcinoma
• Cylindroma
Densely cellular basaloid tumor aggregates which show light and
dark cell types and contain dilated lymphatic channels
CYLINDROCARCINOMA AND
SPIRADENOCARCINOMA
• Clinical features :
• Long standing lesion with recent enlargement ulceration , pain
• Common disparity between high grade appearance of tumor
and lack aggressive behavior
• Histopathologic features :
• Remnant of benign cylindroma or spiradenoma
• Anaplastic epithelium in sheets or nests
• Epitheloid , stellate , or fusiform tumor cells with pronounced
cytologic atypia
• Resemblance to squamous cell carcinoma , adenosquamous
carcinoma , adenocarcinoma , clear cell adenocarcinoma
Pattern 4 : tadpoles /paisley tie
• SYRINGOMA
• MICROCYSTIC ADNEXAL CARCINOMA
SYRINGOMA
• Clinical features :
• Usually multiple
• Plaquelike , milia like , linear and eruptive variants
• Upper cheeks , below eyelids , genitalia , thighs
• Small , discrete , whitish or yellowish papules , 1-4 mm in
diameter
• Histologic features :
• Superficial dermal well defined tumor
• Small tubule or epithelial aggregates , often comma shaped
• Central lumina with luminal cuticle
• Polygonal or flattened tumor cells with eosinophilic or clear
cytoplasm
• Absence of cytologic atypia , mitoses and infiltrative growth
• Differential diagnosis:
• Basal cell carcinoma
• Desmoplastic trichoepithelioma
• Microcystic adnexal carcinoma
SYRINGOMA : small symmetrical tumor in the superficial dermis , tumor is
comprised of cuboidal cells arranged in cords m ducts , tubules and cyst
MICROCYSTIC ADNEXAL CARCINOMA
• CLINICAL FEATURES :
• Adults , age 20-76 years
• Face , especially upper lip , axilla
• Slowly developing indurated plaque or nodule
• Skin colored , yellowish
• Local recurrence common
• Histopathologic features :
• Small epithelial aggregates with keratinous cysts , especially
superficially
• Solid epithelial islands and cords , some with lumina .
• Fibrotic to densely sclerotic stroma
• Deeply invasive with frequent infiltration of subcutis , skeletal
muscle , and nerve
• Minimal or low grade atypia
• Mitotic figures generally uncommon
• Differential diagnosis :
• Syringoma
• Desmoplastic trichoepithelioma
• Morpheaform basal cell carcinoma
MICROCYSTIC ADNEXAL CARCINOMA
PATTERN 5 : CYSTIC SPACES AND
PAPILLARY PROJECTIONS
• SYRINGOCYSTADENOMA PAPILLIFERUM
• HIDRADENOMA PAPILLIFERUM
• DIGITAL PAPILARY ADENOCARCINOMA
SYRINGOCYSTADENOMA PAPILLIFERUM
• CLINICAL FEATURES :
• Head and neck , especially scalp
• Solitary verrucous like plaque or nodule
• Often moist or oozing surface
• Often 2-3 cm
• Frequently congenital and associated with nevus sebaceous
• Histopathologic features
• Epidermal cystic invagination lined by squamous epithelium
with transition to apocrine epithelial lining with 2 cell layers
• Often verrucous epidermal surface
• Cystic invagination contains papillary projections lined by
luminal columnar cells and inner cuboidal cells
• Decapitation secretion
• The stroma of the papillary epithelium strictures contains
numerous plasma cells
• Background nevus sebaceous common
At scanning magnification, the neoplasm shows papillary formations in the superficial areas and tubular
structures involving the full thickness of the dermis. (b) Some of the tubular structures also show
papillary formations within their lumina
HIDRADENOMA PAPILLIFERUM
• CLINICAL FEATURES :
• Women almost exclusively
• Vulva rarely other sites such as breast ,eyelid , ear canal
• Dome shaped nodule with occasional bleeding pain usually
solitary
• Histopathologic features
• Well circumscribed dermal nodule , solid , cystic
• Usually no epidermal connection
• Complex pattern of anastomosing papillary structures , tubules
• Epithelial lining with myoepithelial cells and luminal columnar or
cuboidal cells
• Decapitation secretion
• Occasion al slight nuclear pleomorphism , rare mitoses
• Differential diagnosis
• Syringocystadenoma papilliferum
• Tubular papillary adenoma
HIDRADENOMA PAPILLIFERUM : intradermal
apocrime tumor spears to be floating within its
own cystic space.
Frondlike growth and decapitation
secretion are apparent
DIGITAL PAPILLARY ADENOCARCINOMA
• CLINICAL FEATURES
• All ages
• Digits palms , soles
• Firm nodules
• Histopatholohic features
• Micropapillary projecting into cystic spaces
• Solid nests and tubules composed of polygonal cells
• Infiltration of surrounding tissue
• Nucelar features varying from dispersed chromatin and small nucleoli to vesicular nuclei
with prominent nucleoli
• Atypia may be minimal or absent
• Differential diagnosis:
• Hidradenoma
DIGITAL PAPILLARY ADENOCARCINOMA :
Dermal cystic structure containing solid
nests of tumor cells and papillary features
Infolding of papillary epithelial structures
into cystic spaces lined by cuboidal to
columnar epithelial cells
PATTERN 6 : DERMAL NODULE WITH
VARIABLE MIXTURE OF CORDS/ CHAINS
AND CHONDROMYXOID STROMA
• MIXED TUMOR ( CHONDROID SYRINGOMA )
• MYOEPIHELIAL CARCINOMA /MALIGNANT MIXED TUMOR
• METASTATIC TUMOR VERSUS PRIMARY CUTANEOUS ADNEXAL
NEOPLASMS
CHONDROID SYRINGOMA
• CLINICAL FEATURES :
• Head and neck , especially face
• Men > women
• Firm dermal or subcutaneous nodule
• Histopathologic features :
• Well circumscribed dermal or subcutaneous lobular tumor
• Only rare epidermal connection
• Stromal component : variable chondroid , mucinous hyalinized
or osteoid matrix
• Epithelial component heterogenous : eccrine , apocrine ,
sebaceous , pilar , simple glandular or squamous differentiation
• Often complex pattern of anastomosing tubular lumina lined by
1 or 2 cell layers that are cuboidal or columnar ; rarely small
round tubular lumina lined by cuboidal epithelium
• Occasional prominent cystic spaces
• Differential diagnosis :
• Cutaneous chondroma
• Hidradenoma
MYOEPITHELIAL CARCINOMA /
MALIGNANT MIXED TUMOR
• Occurs mostly in elderly
• No predilection site
• A diagnosis can only be made if a identifiable preexisting benign
component of mixed tumor is seen
• Histopathologic features
• The remnants of benign neoplasm are either juxtaposed or blend gradually
with malignant tissue
• The malignant component shows heterogeneity
• It has different pattern
• Adenocracinoma ( apocrine feature )
• Myoepithelial carcinoma
• Carcinoma NOS
HAIR FOLLICLE TUMORS
TRICHOADENOMA
• Clinical features :
• Usually adults
• Head , neck and trunk
• Nondescript papule < 1 cm
• Histopathological features :
• Dome shaped
• Symmetric
• Keratinous cysts lined by uniform cuboidal cells
• Eosinophilic cor clear cytoplasm
• Granular layer
• No basaloid epithelium
• Differential diagnosis :
• Syringoma
• Desmoplastic trichoepithelioma , conventional trichoepithelioma
• Microcystic adnexal carcinoma
• Tumour of the follicular infundibulum
• Basal cell carcinoma
A) Trichoadenoma. (B) There are multiple ‘cystic structures’
resembling cross-sections of the infundibular portion of hair follicles
BENIGN FOLLICULAR NEOPLASMS WITH
GERMINATIVE-TYPE DIFFERENTIATION
• TRICHOFOLLICULOMA
• Trichofolliculoma is a rare pilar tumor, intermediate in
differentiation between a hair follicle nevus and a trichoepithelioma
.
• It usually presents as a solitary tumor, approximately 0.5 cm in
diameter, on the head and neck, usually the face.
• There are one or several dilated follicles from which radiate
numerous small follicles of varying degrees of maturity
• Trichofolliculomas have a relatively cellular connective tissue
stroma.
• This complex pattern is quite different from the hair follicle
nevus which is composed of mature vellus follicles.
• Merkel cells are found in the outer sheath of the small follicles
• The central follicle, which opens onto the surface, usually
contains keratinous material and sometimes vellus hairs.
• The follicles that branch off the central follicle may in turn give
rise to secondary or even tertiary follicles.
• Sometimes only rudimentary pilar structures or epithelial cords
are formed.
• In older lesions, catagen and telogen follicles are present
A) Trichofolliculoma. (B) Small follicles with variable maturity radiate rom a larger
central follicle
TRICHOEPITHELIOMA
• CLINICAL FEATURES :
• Solitary or multiple
• Head and neck ,especially face
• Skin – colored papule or nodule , pearly appearance
• Usually < 1 cm
• Histopathologic features
• Oragnoid arrangement of mature collagenous hypocellular stroma about
lobules of uniform basalod cells , well demarcated from surrounding
dermis
• Basaloid cells tend to show peripheral palisading of the nuclei , lacelike or
cribriform in patterns and hair matrix like differentiation
• Keratinous microcytst frequent
• Often hair papilla like structures in stroma adjacent to hair
matrical like epithelium
• Minimal or no mitotic figures and necrotic cells
• Differential diagnosi
• Trichofolliculoma
• Basal cell carcinoma
(A) Trichoepithelioma. There are multiple nests of basaloid cells, with
some showing abortive hair follicle differentiation. (B) Early follicular stromal
induction is present. (H&E)
DESMOPLASTIC TRICHOEPITHELIOMA
CLINICAL FEATURES :
Young to middle aged adults
Women more often than men
Central face , especially the cheeks
Solitary , often skin colored or slightly yellowish plaque
Raised borders and slightly depressed central area
Firm or scar like
• Histopathologic features :
• Discoid lesion in upper dermis with well defined margins
• Narrow linear or slightly branching cords of compact polygonal
or basaloid cells
• Keratinous microcysts often filled with calcified material
• Densely collagenized stroma surrounds epithelial elements
• Dystrophic calcification
• Foreign body giant cell reaction to keratin
• Differential diagnosis :
• Syringoma
• Microcystic adnexal carcinoma
Desmoplastic
trichoepithelioma :
thin strands of
basaloid epithelium
with keratinous cyts ,
sclerotic stroma and
calcified material
PILOMATRICOMA
• Clinical features :
• Children and adolescents , but any age may be affected
• Head and neck most common
• Solitary slow developing hard nodule , usually deeply seated
• Histopathologic features :
• Well defined lobular tumor in dermis or subcutis
• Initially the tumor may be cystic with infundibular and
germinative matrical cellular components
• Germinative-matrical cells are uniform basaloid cells with
monotonous round nuclei, dark chromatin, and small nucleoli
• Prominent mitotic activity
• Transition of matrical epithelium to "ghost" or “shallow" cells
that exhibit an imprint of a nucleus that has been lost
• Formation of hard nail-like keratin
• Progressive loss of basaloid epithelium
• Foreign body giant cell reaction to keratin
• Calcification, ossification
• They resemble the cells of a basal cell carcinoma. They are
sometimes the predominant cell in lesions removed from elderly
patients.
• The term ‘proliferating pilomatricoma’ has been proposed for
this variant
• Calcification occurs in more than two-thirds of the tumors and is
usually in the shadow cells
• There are masses of epithelial cells of various shapes, with an
intervening connective tissue stroma containing blood vessels, a
mixed inflammatory cell infiltrate, foreign body giant cells, and
sometimes hemosiderin, melanin, bone, and rarely amyloid.
(A) Pilomatricoma. (B) There are two cell types present – nests of basaloid cells and shadow cells.
The lesion is partly cystic.
Pilomatricoma. Round
cystic tumor with basaloid
epithelial lining and
eosinophilic keratinous
contents.
Trichoblastoma
Clinical Features
Adults
Women as often as men
Almost any location, especially the face and scalp
Usually does not involve distal extremities
Solitary nondescript papule or nodule
Usually <2 cm, but may be giant
Histopathologic Features
Well demarcated from surrounding tissue
Symmetric
Basaloid epithelial proliferation in cords, sheets, or discrete clusters
Fibrotic investment of epithelium
Follicular germinative epithelium
• Peripheral palisading of nuclei
• Follicular differentiation resembling hair bulbs and papillae
• Keratinous cysts on occasion
• Fibrotic stroma
• Occasional necrosis
• Limited numbers of mitoses
• Differential Diagnosis
• Basal cell carcinoma
Trichoblastoma. This basaloid tumor resembles basal cell carcinoma.There is some trichogenic
differentiation and stromal induction.
This striking simulation of hair matrix and hair papilla by
the mesenchymal stroma and
basaloid epithelium in hair germinative tumors is referred
to as a papillary mesenchymal body.
Pigmented trichoblastoma. There is focal stromal induction with the formation of primitive
follicular structures.
Approach to skin adnexal tumors
GENERAL APPROACH TO ADNEXAL
TUMORS
ADNEXAL
TUMORS
WITH
EPIDERMAL
CONNECTION
WITH NO
EPIDERMAL
CONNECTION
SEBACEOUS
TUMORS
CYSTS
PREDOMINANTLY WITH
EPIDERMAL CONNECTION
BASALOID ( BLUE) TUMOR
+ CUTICLE FORMATION
POROMA
POROCARCINOMA
+CLEAR OR EOSINOPHILIC
CYTOPLASM + PERIPHERAL
NUCLEAR PALISADING
TRICHILEMMOMA
+ DILATED FOLLICULAR
ORIFICE
TRICHOFOLLICULOMA
DILATED PORE OF WINER
PILAR SHEATH
ACANTHOMA
DUCTS , GLANDS AND
PAPILLAE
SYRINGOCYSTADENOMA
PAPILLIFERUM
VACULATED CYTOPLASM
SEBACEOUS TUMOR
TUMOR WITH NO EPIDERMAL CONNECTION
PREDOMINANTLY
WITH NO EPIDERMAL
CONNECTION
BASALOID TUMOR
CLEAR CELLS AND
EOSINOPHILIC
CYTOPLASM +/-
CYSTIC CHANGES
DUCTAL / GLANDULAR
FORMATION
PREDOMINANTLY NO
EPIDERMAL
CONNECTION
PERIPHERAL NUCLEAR
PALISADING
TRICHOEPITHELIOMA
TRICHOBLASTOMA
TWO CELL TYPES +
INTERMINGLED
LYOMPHOCYTES
SPIRADENOMA
CYLINDROMA
CUTICLE ( SMALL
DUCTS) FORMATION
DERMAL DUCT
TUMOR
GHOST CELLS
PILOMATRIXOMA
VACOULATED
CYTOPLASM
SEBACEOMA
SEBACEOUS
CARCINOMA
BASALOID TUMOR
EXCLUDE BASAL CELL
CARCINOMA
PREDOMINANTLY WITH
NO EPIDERMAL
CONNECTION
CLEAR AND EOSINOPHILIC
CYTOPLASM +/- CYSTIC
CHANGE
HIDRADENOMA
HIDRADENOCARCINOMA
EXCLUDE
METABOLIC RENAL
CELL ACRCINOMA
TUMORS WITH SEBACEOUS DIFFERENTIATION

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skin adnexal ppt.pptx

  • 2. INTRODUCTION • Skin adnexal tumours can be benign or malignant lesions with differentiation similar to one or more types pf adnexal epithelium found in normal skin • Skin appendages are derived from the ectoderm • These lesions are divided into three major groups on the basis of types of adnexal structures : • Hair follicles • Sebaceous glands • Apocrine / eccrine glands
  • 3. Normal histology of skin appendages • Normal skin adnexal structures include hair follicles with associated apocrine and sebaceous glands • The eccrine glands attaches directly to the epidermis
  • 4. PILOSEBACEOUS UNIT • Hair follicle is tubular invagination from the epidermis , responsible for formation if hair a highly modified keratinised structure • Highly vascular connective tissue papillae enclosed by bulbous expansion are located in the reticular dermis or in the superficial subcutaneous fatty tissue and from lower portion of the hair follicle • the hair shaft consists of an innermost medulla surrounded by a broad , highly keratinised cortical layer and an outermost thin layer of overlapping keratin
  • 5.
  • 6.
  • 7.
  • 9. SWEAT GLANDS • There are two types of sweat glands • Apocrine sweat glands • Eccrine sweat glands
  • 12. • Secretion is due to separation of the apical cap which was formed during the maturation of gland
  • 14. SEBACEOUS TUMORS Sebaceous proliferations are usually easy to recognize because of the vacuolated bubbly , mature sebocytes that are present in varying proportions in the most sebaceous lesions Mature sebocytes will possess 3 criteria: • Sharply marginated round cytoplasmic vacuoles • Vacuoles that are optically clear ( white) • Vacuoles that scallop / indent into nuclear membrane
  • 15. Sebaceous hyperplasia Clinical Features • Older individuals • Face, mammary areola, genital skin • Yellowish to tan papules, often umbilicated • Rare linear or giant forms Histopathologic Features • Single follicular canal opens to umbilicated epidermal surface • Four or more sebaceous lobules attached to central infundibulum of sebaceous follicle • Fully mature sebaceous lobules composed of sebocytes with compact nuclei and abundant multivacuolated clear cytoplasm
  • 16. Sebaceous hyperplasia: the sebaceous lobules drain through short ductules into the central duct.
  • 17. .
  • 18. Sebaceoma • Sebacoma presents as a yellow-to-orange or flesh-colored papule, nodule or tumor measuring approximately 1–3 cm in diameter • These tumors are usually solitary , flesh colored to yellowish papulonodules on the face or scalp • They may be multiple if they are associated with muir torre syndrome • Histopathology : • There are multiple nests of basaloid cells with random mixture of sebaceous cells wither solitary or in clusters • The tumor is centred on the upper and mid dermis but some nests may be continuous with the basal layer of the epidermis • The small basaloid cells of the tumor outnumber the mature sebaceous component • There are scattered mitoses but the tumor lacks the atypia of sebaceous carcinoma
  • 19. Sebaceoma: there is a multinodular dermal tumor showing multiple points of origin/contact with the epidermis.
  • 20. Sebaceoma: (A) the tumor consists of a random admixture of basaloid cells and mature sebocytes; (B) in this field, there are two mitoses. There is no significant atypia.
  • 21. • Differential diagnosis : • Sebaceoma can be distinguished from sebaceous adenoma in which a lobular architecture with distinct and regular maturation (mimicking the normal sebaceous gland) is typically present. • Sebaceous adenoma generally presents as a solitary nodular lesion in the superficial dermis, frequently replacing the overlying epidermis in whole or in part. • It should be noted, however, that focal sebaceous adenoma-like features may sometimes be seen in a background of more typical sebaceoma
  • 22. Sebaceous adenoma • Clinical Features • Patient often older than 50 years of age • Head and neck, especially face • Yellowish nodule • Usually <1 cm but can be :l:S cm • Association with Muir-Torre syndrome (sebaceous neoplasms, squamous cell carcinomas, and visceral carcinomas [laryngeal and gastrointestinal)
  • 23. • Histopathologic Features • Classical type • Well-defined enlarged sebaceous lobules • Frequent attachment to epidermis with epidermal thinning • Fully mature sebocytes • Lobules may contain ductlike structures • Variant type (Muir-Torre) • Sharp demarcation of lobules may be lacking Lobules show admixture of peripherally located basaloid epithelium (50%) centrally mature sebocytes
  • 24. • Basaloid epithelium may show slight nuclear pleomorphism, distinct nucleoli, and occasional mitoses • Differential Diagnosis • Sebaceous hyperplasia • Sebaceoma • Basal cell carcinoma with sebaceous differentiation
  • 25. Sebaceous adenoma: (A) this example has been shelled out. Note the circumscribed border; (B) there is a peripheral layer of basophilic germinative cells and inner sebaceous cells with bubbly cytoplasm and crenated nuclei.
  • 26. Malignant sebaceous tumors • Clinical Features • Middle-aged and elderly patients (mean age, 62 years) • Predilection for Asians • Ocular (upper eyelids) more often than extraocular sites (head and neck more often than trunk, genitalia, extremities) • Nontender mass
  • 27. • Histopathologic Features • Bowenoid or pagetoid pattern of atypical epithelial cells within epidermis or conjunctiva ,epithelium, or both • Lobular dermal aggregates of variably atypical polyhedral cells • Central necrosis ("comedo" pattern) common • Well-differentiated tumors: cells with abundant multivacuolated cytoplasm, vesicular nuclei, and discernible nucleoli
  • 28. • Poorly differentiated tumors: nondescript cells with high nucleocytoplasmic ratios, prominent nuclear pleomorphism, prominent nucleoli, prominent mitotic activity • Basaloid SC: small cells with scanty cytoplasm, peripheral palisading, nuclear anaplasia • Squamoid SC: prominent squamous metaplasia with keratin pearls • Sarcomatoid SC: spindle cell features
  • 29. • lmmunohistochemistry • EMA+, Androgen receptor+, Adipophilin+, • Factor XI Ila (clone AC-1A1 )+ • BerEp4-, CEA-, pan CK+, CK7+, p40+, p63+, • CD10+, KIT+, Melan-A • Differential Diagnosis • Sebaceous adenoma • Sebaceoma • Clear cell squamous cell carcinoma • Clear cell basal cell carcinoma • Balloon cell melanoma • Trichilemmal carcinoma • Merkel cell carcinoma
  • 30. • Sebaceous carcinoma. (A} Small, well· differentiated tumor. Note lobular architecture with discrete tumor lobules separated by a nondesmoplastic fibrousstroma. • {B) A large proportion of clear cells are observed in this well-differentiated variant
  • 31.
  • 32. Sebaceous neoplasms and muir torre syndrome • Some sebaceous adenomas, sebaceomas, and sebaceous carcinomas are associated with MTS. • Sebaceous hyperplasia has no association with this syndrome, nor does nevus sebaceus. • Muir-Torre syndrome is a variant of hereditary nonpolyposis colorectal cancer syndrome (also referred to as Lynch syndrome). • It is the result of a germline mutation in one of several DNA mismatch repair (MMR) genes, most notably MLH1, MSH2, MSH6, and PMS2. • Unlike classic Lynch syndrome, where MLH1 mutations predominate, MSH2 is the most common germline-mutated MTS-associated gene. • A second hit to the other allele of the mutated mismatch repair gene results in microsatellite instability and may lead to subsequent development of cancer.
  • 33. • MMR protein expression in sebaceous lesions can be assessed by IHC. • Like in classic Lynch syndrome, because MMR proteins are paired in the cell, loss of one may affect the presence of another. • MLH1 is paired with PMS2; as the dominant partner, if MLH1 is lost, PMS2 is also lost (but not vice versa). • Similarly, MSH2 and MSH6 are partners; as the dominant partner, if MSH2 is lost, then MSH6 is also lost (but not vice versa). • The combination of positive and negative staining should yield enough information to identify the putative defective gene
  • 34. • solid sheets of basaloid cells in some lobules or an intermingling of these cells and sebaceous cells without any orderly maturation. • Sometimes the tumors resemble a basal cell carcinoma but with focal sebaceous differentiation. • Mucinous and cystic areas may be present • Cystic components are important component of this syndrome • All sebaceous tumors should be screened for the presence of MSH-2, MSH-6, MLH-1, and PMS-2, the respective gene products of MSH2, MSH6, MLH1, and PMS2
  • 35. • The diagnosis of Muir–Torre syndrome is made when nuclear staining for the particular gene product is absent in the tumors • The cells express epithelial membrane antigen and nuclear androgen receptor
  • 36.
  • 37. Immunohistochemistry of sebaceous tumors Immunohistochemistry Target action Function EMA Strong positivity and highlights vacuoles of more mature sebocytes. Recognizing vacuolated patterns on EMA staining is the most important feature Adipophilin Strongly highlights cytoplasmic vacuoles in more mature sebocytes P63 and p40 P63 and p40 are expressed in the basaloid germinative cells of normal sebaceous gland CK7 Most sebaceous tumours show CK 7 positivity CEA Sebaceous tumours are negative for CEA Ber-EP4 Negative in sebacoma positive in basal cell carcinoma FACTOR XIII a ( iclone AC-1A1) Nuclear staining of normal and neoplastic sebocytes
  • 38. USEFUL HISTOLOGICAL FEATURES FOR DISTINGUISHING BETWEEN SEBACOMA AMD BASAL CELL CARCINOMA WITH SEBACEOUS DIFFERENTIATION FEATURES SEBACOMA BCC WITH SEBACEOUS DIFFERENTIATION OVERALL MORPHOLOGY SIMILAR TO SEBACEOUS ADENOMA BUT WITH MORE BASALOID COMPONENT Similar to classical BCC, but with a component of sebaceous differentiation Main components Aggregates of basaloid germinative cells admixed with single units or clusters of mature vacuolated sebocytes Aggregate of follicular germinative basaloid cells Architectural pattern Benign malignant Cytological features Monomorphous basaloid cells, with small oval nuclei and non-prominent nucleoli Pleomorphic basaloid cells, with slightly elongated nuclei Mitotic activity Mild/absent Brisk Sebaceous differentiation Prominent Focal and associated with apocrine differentiation in many cases Peripheral palisading Artefactual clefting Absent Absent Present Present Other associated features Sebaceous duct-like structures, rare squamous differentiation, and dense eosinophilic dermal sclerosis Sebaceous duct-like structures, individual cell necrosis, keratinization and mucinous stroma
  • 39. Tumors with focal sebaceous differentiation • These tumors show sebaceous differentiation or sebaceous glands can be seen in the following : • Basal cell carcinoma • Squamous cell carcinoma • Trichoblastoma • Seborrheic keratosis • Dermatofibroma • Reticulated acanthoma
  • 40. Trichoblastoma with sebaceous differentiation It is characterised by sebocytes and sebaceous duct like structures within basaloid aggregations of a large nodular type of trichoblastoma seborrhic keratosis with sebaceous differentiation Areas of seborrheic keratosis with admixed sebocytes occurring in clusters or as a single cells Microcysts with variable resemblance to sebaceous ducts are usually present They are much smaller than horn cysts of seborrheic keratosis Verruca vulgaris with sebaceous differentiation : Rare entity Sometimes focal apocrine differentiation may also be present Reticulated acanthoma with sebaceous differentiation have been called as superficial epithelioma with sebaceous differentiation Apocrine poroma with sebaceous resembles eccrine poroma
  • 41. Sweat gland tumors • Sweat gland tumors have been divided into apocrine and eccrine • The distinction between apocrine and eccrine is difficult because the ducts of each gland type are identical • Fulton et al had arranged sweat gland tumors into 6 groups based on common histologic patterns
  • 42. PATTERN 1 : DERMAL CYST WITH DOUBLE CUBOIDAL / COLUMNAR LINING HIDROCYSTOMA CYSTADENOMA
  • 43. HIDROCYSTOMA • They are simplest benign sweat gland tumors • They present as small translucent papules on the upper cheek near the eye • The cysts are unilocular and are lined by two layers of cuboidal epithelium • CK 7 , 8 and 19 are present in these tumors , on the basis of this they were regarded as being of eccrine origin
  • 44. The cysts are lined by two layers of cells: (1) an inner lining of large columnar cells with eosinophilic cytoplasm often showing luminal decapitation secretion (2) an outer flattened layer of myoepithelial cells.
  • 45. CYSTADENOMA : • When the lining of hidrocystoma becomes thicker or more complex • Then these terms are called as cystadenoma
  • 46. PATTERN 2 : SOLID PINK /CLEAR /SQUAMOID PROLIFERATION IN EPIDERMIS AND / OR DERMIS +/- CYSTIC CHANGE • ACROSPIROMAS ( HIDROACANTHOMA SIMPLEX , POROMA , DERMAL DUCT TUMOR , HIDRADENOMA ) AND THEIR MALIGNANT COUNTER PARTS
  • 47. Hidroacanthoma simplex • Hidroacanthoma simplex (intraepidermal eccrine poroma) is a solitary plaque or nodular lesion found particularly on the extremities and the trunk • It arises throughout adult life, and there is an equal sex incidence. Clinically, it resembles a seborrheic keratosis or basal cell carcinoma. • Histopathology • Hidroacanthoma simplex is composed of well-circumscribed nests of cuboidal to oval basaloid cells within the epidermis, resembling those seen in eccrine poroma
  • 48.
  • 49. POROMA • Poroma is a benign adnexal tumor with differentiation towards the intradermal portion of the sweat apparatus • It is divided into : • Eccrine poroma • Dermal eccrine poroma • Hidracanthoma simplex ( intraepidermalporoma) • Syringoacanthoma • Syringofibroadenoma • These lesions contains two or three histologically components • Hidroacanthoma simplex • Eccrine poroma • Dermal duct tumor
  • 50. Eccrine poroma • Clinical presentation : • Solitary , pink or red exophytic nodule • Plantar or palmar skin on the lower extremities and hands • Age group : middle aged or elderly • Histopathology • Eccrine poroma is a circumscribed tumor composed of cords and broad columns of uniform basaloid cells extending into the dermis from the undersurface of the epidermis • Cells are PAS positive and diastase sensitive
  • 51.
  • 52. DERMAL DUCT TUMOR • Tumor composed of basaloid cells , like a eccrine poroma but located in the dermis • Clinical : • Papule, plaque or nodule in the lower limbs or head and neck region • Histopathology : • Tumor is composed of islands of basaloid tumor cells within the dermis • Duck like structure are prominent in many of the nests and tumor may connect with a normal appearing eccrine duct • Epidermal connection is often found in multiple sections examined
  • 53. • Cells are PAS positive , sometimes melanin pigments are found • Clear cell variant : • Multiple solid aggregates of clear cells involving the dermis • Ductal structures are also present
  • 54.
  • 55. • Differential diagnosis : • Porocarcinoma : infiltrative growth and areas of spontaneous necrosis is seen
  • 56. HIDRADENOMA ( ACROSPIROMA) • There are two variants of hidradenoma • Apocrine hidradenoma • Eccrine hidradenoma ( poroid hidradenoma ) • Apocrine hidradenoma is composed of clear , polygonal and mucinous cells • Eccrine hidradenoma consist of poroid and cuticular cells
  • 57. Apocrine hidradenoma • Clinical presentation : • Solitary nodules 2 or 3 cm in diameter • Predominantly seen in females • There is no site predilection • They may be associated with t (11;19) has been reported in breast parenchyma
  • 58. • HISTOPATHOLOGY : • Hidradenomas are circumscribed non encapsulated multilobular tumors centred on the dermis and sometimes extends into subcutis • Epidermal connections are present • Tumor cells may be round , fusiform or polygonal in shape are biphasic in cytoplasmic architecture • Some cells show clear cell change • Duct like structures are often present in the tumor . • Some resemble eccrine or apocrine ducts • The stroma between lobules varies from thin , delicate , vascularized collagen
  • 59. • Immunohistochemistry : • Low molecular weight cytokeratin (CAM 5.2) • Some also express CEA and EMA • Smooth muscle actin and S100 protein were coexpressed
  • 60. Hidradenoma ( poroid hidradenoma ) • Eccrine hidradenoma ( poroid hidradenoma ) is circumscribed , non encapsulated dermal tumor composed of poroid and cuticular cells • Ductal structures may form , particularly within the zones of cuticular cells • It lacks polygonal , clear and mucinous cells of apocrine variant
  • 61. Hidradenoma shows clear cells . The nuclei are smaller than in eosinophilic cells
  • 62. Poroid hidradenoma. This lesion has the cytological characteristics of a poroma, and it lacks polygonal, clear, or mucinous cells. Ductal structures ca be identified within the tumor
  • 63. MALIGNANT ACROSPIROMA • These tumors posses architectural similarities to their benign counterpart • They show cytologic atypia , brisk or atypical mitotic activity and /or infiltrative growth pattern • Eg : porocarcinoma , hidradenocarcinoma
  • 64. POROCARCINOMA • CLINICAL FEATURES : • Older individuals , often > 60 years • Lower extremities , head and neck , upper extremities , trunk • Verrucous papule or nodule , may ulcerate • High rate of recurrence • Regional lymph node metastases • Tendency to multiple multiple epidermotropic metastases
  • 65. • Histologic features : • Features of poroma • Infiltrative features • Often desmoplastic stroma is seen • Tumor necrosis • Cytologic atypia and mitoses is seen • Extensive clear cell change is seen
  • 66. • Differential diagnosis : • Eccrine poroma • Squamous cell carcinoma • Hidradenocarcinoma • Trichilemmal carcinoma • Amelanotic melanoma
  • 67. Porocarcinoma : lobular aggregates of atypical cuboidal tumor cells extend from epidermis into dermis Scant solitary poroid carcinomatous tumor nests within the epidermis are associated with dermal invasion by tuor aggregates with conspicuous cytologic
  • 68. HIDRADENOCARCINOMA • Formerly named as malignant acrospiroma • Malignant counterpart of hidradenoma • Clinical features : • Nodules involving head and neck area , the extremities • Tumor may ulcerate • Associated with frequent metastases • Histopathologic features : • Dermal based tumid composed of lobules of polygonal eosinophilic or clear cells
  • 69. • Occasional basaloid and squamous foci • Ductal structures • Infiltrative growth pattern • Three morphologic variants : • Polypoid configuration of tumor • Sclerosing variant with marked desmoplasia • Comedo variant showing central necrosis within lobular epithelial aggregates
  • 70. • Differential diagnosis : • Porocarcinoma • Squamous cell carcinoma • Sebaceous carcinoma Large lobular dermal tumor with superficial cystic spaces and comprised of irregular nests of basaloid tumor cells
  • 71. Large lobular aggregates of tumor cells exhibit variable clear cell change and focal necrosis
  • 72. PATTERN 3 : BLUE BASALOID PROLIFERATION IN DERMIS • SPIRADENOMA • CYLINDROMA
  • 73. CYLINDROMA • Clinical features : • Head and neck especially scalp • Multiple tumors ( turban tumors) • Autosomal dominant • Association with spiradenomas and trichoepitheliomas • Histopathologic features : • Mosaic or jigsaw puzzle patter of tumor islands • Tumor aggregates delimited by basement membrane material that also results in hyaline droplets within aggregates
  • 74. • Basaloid tumor aggregates with 2 cellular populations • Outer layer composed of small , round cells with scant cytoplasm • Inner layer comprised of larger polygonal cells with more abundant cytoplasm • Irregular pattern at periphery of tumor • Occasional mitotic figures • Differential diagnosis : • Basal cell carcinoma • Spiradenoma
  • 75.
  • 76.
  • 77. SPIRADENOMA • CLINICAL FEATURES Trunk , ventral surfaces Skin colored or bluish white cystic or spongelike consisitency Painful or tender Histopathology : Rounded tumor lobules often large and few in number No epidermal connection or jigsaw puzzle pattern Tumor lobules delimited by basement membrane material and contain hyaline droplets Smaller outer cells Large inner polygonal cells May contain small ductular structures
  • 78. • Differential diagnosis • Basal cell carcinoma • Cylindroma
  • 79. Densely cellular basaloid tumor aggregates which show light and dark cell types and contain dilated lymphatic channels
  • 80. CYLINDROCARCINOMA AND SPIRADENOCARCINOMA • Clinical features : • Long standing lesion with recent enlargement ulceration , pain • Common disparity between high grade appearance of tumor and lack aggressive behavior • Histopathologic features : • Remnant of benign cylindroma or spiradenoma • Anaplastic epithelium in sheets or nests • Epitheloid , stellate , or fusiform tumor cells with pronounced cytologic atypia
  • 81. • Resemblance to squamous cell carcinoma , adenosquamous carcinoma , adenocarcinoma , clear cell adenocarcinoma
  • 82. Pattern 4 : tadpoles /paisley tie • SYRINGOMA • MICROCYSTIC ADNEXAL CARCINOMA
  • 83. SYRINGOMA • Clinical features : • Usually multiple • Plaquelike , milia like , linear and eruptive variants • Upper cheeks , below eyelids , genitalia , thighs • Small , discrete , whitish or yellowish papules , 1-4 mm in diameter
  • 84. • Histologic features : • Superficial dermal well defined tumor • Small tubule or epithelial aggregates , often comma shaped • Central lumina with luminal cuticle • Polygonal or flattened tumor cells with eosinophilic or clear cytoplasm • Absence of cytologic atypia , mitoses and infiltrative growth • Differential diagnosis: • Basal cell carcinoma • Desmoplastic trichoepithelioma • Microcystic adnexal carcinoma
  • 85.
  • 86. SYRINGOMA : small symmetrical tumor in the superficial dermis , tumor is comprised of cuboidal cells arranged in cords m ducts , tubules and cyst
  • 87. MICROCYSTIC ADNEXAL CARCINOMA • CLINICAL FEATURES : • Adults , age 20-76 years • Face , especially upper lip , axilla • Slowly developing indurated plaque or nodule • Skin colored , yellowish • Local recurrence common
  • 88. • Histopathologic features : • Small epithelial aggregates with keratinous cysts , especially superficially • Solid epithelial islands and cords , some with lumina . • Fibrotic to densely sclerotic stroma • Deeply invasive with frequent infiltration of subcutis , skeletal muscle , and nerve • Minimal or low grade atypia • Mitotic figures generally uncommon
  • 89. • Differential diagnosis : • Syringoma • Desmoplastic trichoepithelioma • Morpheaform basal cell carcinoma
  • 91. PATTERN 5 : CYSTIC SPACES AND PAPILLARY PROJECTIONS • SYRINGOCYSTADENOMA PAPILLIFERUM • HIDRADENOMA PAPILLIFERUM • DIGITAL PAPILARY ADENOCARCINOMA
  • 92. SYRINGOCYSTADENOMA PAPILLIFERUM • CLINICAL FEATURES : • Head and neck , especially scalp • Solitary verrucous like plaque or nodule • Often moist or oozing surface • Often 2-3 cm • Frequently congenital and associated with nevus sebaceous
  • 93. • Histopathologic features • Epidermal cystic invagination lined by squamous epithelium with transition to apocrine epithelial lining with 2 cell layers • Often verrucous epidermal surface • Cystic invagination contains papillary projections lined by luminal columnar cells and inner cuboidal cells • Decapitation secretion • The stroma of the papillary epithelium strictures contains numerous plasma cells • Background nevus sebaceous common
  • 94.
  • 95. At scanning magnification, the neoplasm shows papillary formations in the superficial areas and tubular structures involving the full thickness of the dermis. (b) Some of the tubular structures also show papillary formations within their lumina
  • 96.
  • 97. HIDRADENOMA PAPILLIFERUM • CLINICAL FEATURES : • Women almost exclusively • Vulva rarely other sites such as breast ,eyelid , ear canal • Dome shaped nodule with occasional bleeding pain usually solitary • Histopathologic features • Well circumscribed dermal nodule , solid , cystic • Usually no epidermal connection • Complex pattern of anastomosing papillary structures , tubules
  • 98. • Epithelial lining with myoepithelial cells and luminal columnar or cuboidal cells • Decapitation secretion • Occasion al slight nuclear pleomorphism , rare mitoses • Differential diagnosis • Syringocystadenoma papilliferum • Tubular papillary adenoma
  • 99. HIDRADENOMA PAPILLIFERUM : intradermal apocrime tumor spears to be floating within its own cystic space. Frondlike growth and decapitation secretion are apparent
  • 100. DIGITAL PAPILLARY ADENOCARCINOMA • CLINICAL FEATURES • All ages • Digits palms , soles • Firm nodules • Histopatholohic features • Micropapillary projecting into cystic spaces • Solid nests and tubules composed of polygonal cells • Infiltration of surrounding tissue • Nucelar features varying from dispersed chromatin and small nucleoli to vesicular nuclei with prominent nucleoli • Atypia may be minimal or absent • Differential diagnosis: • Hidradenoma
  • 101. DIGITAL PAPILLARY ADENOCARCINOMA : Dermal cystic structure containing solid nests of tumor cells and papillary features Infolding of papillary epithelial structures into cystic spaces lined by cuboidal to columnar epithelial cells
  • 102. PATTERN 6 : DERMAL NODULE WITH VARIABLE MIXTURE OF CORDS/ CHAINS AND CHONDROMYXOID STROMA • MIXED TUMOR ( CHONDROID SYRINGOMA ) • MYOEPIHELIAL CARCINOMA /MALIGNANT MIXED TUMOR • METASTATIC TUMOR VERSUS PRIMARY CUTANEOUS ADNEXAL NEOPLASMS
  • 103. CHONDROID SYRINGOMA • CLINICAL FEATURES : • Head and neck , especially face • Men > women • Firm dermal or subcutaneous nodule • Histopathologic features : • Well circumscribed dermal or subcutaneous lobular tumor • Only rare epidermal connection • Stromal component : variable chondroid , mucinous hyalinized or osteoid matrix
  • 104. • Epithelial component heterogenous : eccrine , apocrine , sebaceous , pilar , simple glandular or squamous differentiation • Often complex pattern of anastomosing tubular lumina lined by 1 or 2 cell layers that are cuboidal or columnar ; rarely small round tubular lumina lined by cuboidal epithelium • Occasional prominent cystic spaces • Differential diagnosis : • Cutaneous chondroma • Hidradenoma
  • 105.
  • 106. MYOEPITHELIAL CARCINOMA / MALIGNANT MIXED TUMOR • Occurs mostly in elderly • No predilection site • A diagnosis can only be made if a identifiable preexisting benign component of mixed tumor is seen • Histopathologic features • The remnants of benign neoplasm are either juxtaposed or blend gradually with malignant tissue • The malignant component shows heterogeneity • It has different pattern • Adenocracinoma ( apocrine feature ) • Myoepithelial carcinoma • Carcinoma NOS
  • 107.
  • 109. TRICHOADENOMA • Clinical features : • Usually adults • Head , neck and trunk • Nondescript papule < 1 cm • Histopathological features : • Dome shaped • Symmetric • Keratinous cysts lined by uniform cuboidal cells • Eosinophilic cor clear cytoplasm
  • 110. • Granular layer • No basaloid epithelium • Differential diagnosis : • Syringoma • Desmoplastic trichoepithelioma , conventional trichoepithelioma • Microcystic adnexal carcinoma • Tumour of the follicular infundibulum • Basal cell carcinoma
  • 111. A) Trichoadenoma. (B) There are multiple ‘cystic structures’ resembling cross-sections of the infundibular portion of hair follicles
  • 112. BENIGN FOLLICULAR NEOPLASMS WITH GERMINATIVE-TYPE DIFFERENTIATION • TRICHOFOLLICULOMA • Trichofolliculoma is a rare pilar tumor, intermediate in differentiation between a hair follicle nevus and a trichoepithelioma . • It usually presents as a solitary tumor, approximately 0.5 cm in diameter, on the head and neck, usually the face. • There are one or several dilated follicles from which radiate numerous small follicles of varying degrees of maturity
  • 113. • Trichofolliculomas have a relatively cellular connective tissue stroma. • This complex pattern is quite different from the hair follicle nevus which is composed of mature vellus follicles. • Merkel cells are found in the outer sheath of the small follicles
  • 114. • The central follicle, which opens onto the surface, usually contains keratinous material and sometimes vellus hairs. • The follicles that branch off the central follicle may in turn give rise to secondary or even tertiary follicles. • Sometimes only rudimentary pilar structures or epithelial cords are formed. • In older lesions, catagen and telogen follicles are present
  • 115. A) Trichofolliculoma. (B) Small follicles with variable maturity radiate rom a larger central follicle
  • 116. TRICHOEPITHELIOMA • CLINICAL FEATURES : • Solitary or multiple • Head and neck ,especially face • Skin – colored papule or nodule , pearly appearance • Usually < 1 cm • Histopathologic features • Oragnoid arrangement of mature collagenous hypocellular stroma about lobules of uniform basalod cells , well demarcated from surrounding dermis • Basaloid cells tend to show peripheral palisading of the nuclei , lacelike or cribriform in patterns and hair matrix like differentiation • Keratinous microcytst frequent
  • 117. • Often hair papilla like structures in stroma adjacent to hair matrical like epithelium • Minimal or no mitotic figures and necrotic cells • Differential diagnosi • Trichofolliculoma • Basal cell carcinoma
  • 118. (A) Trichoepithelioma. There are multiple nests of basaloid cells, with some showing abortive hair follicle differentiation. (B) Early follicular stromal induction is present. (H&E)
  • 119. DESMOPLASTIC TRICHOEPITHELIOMA CLINICAL FEATURES : Young to middle aged adults Women more often than men Central face , especially the cheeks Solitary , often skin colored or slightly yellowish plaque Raised borders and slightly depressed central area Firm or scar like
  • 120. • Histopathologic features : • Discoid lesion in upper dermis with well defined margins • Narrow linear or slightly branching cords of compact polygonal or basaloid cells • Keratinous microcysts often filled with calcified material • Densely collagenized stroma surrounds epithelial elements • Dystrophic calcification • Foreign body giant cell reaction to keratin
  • 121. • Differential diagnosis : • Syringoma • Microcystic adnexal carcinoma
  • 122. Desmoplastic trichoepithelioma : thin strands of basaloid epithelium with keratinous cyts , sclerotic stroma and calcified material
  • 123. PILOMATRICOMA • Clinical features : • Children and adolescents , but any age may be affected • Head and neck most common • Solitary slow developing hard nodule , usually deeply seated • Histopathologic features : • Well defined lobular tumor in dermis or subcutis • Initially the tumor may be cystic with infundibular and germinative matrical cellular components
  • 124. • Germinative-matrical cells are uniform basaloid cells with monotonous round nuclei, dark chromatin, and small nucleoli • Prominent mitotic activity • Transition of matrical epithelium to "ghost" or “shallow" cells that exhibit an imprint of a nucleus that has been lost • Formation of hard nail-like keratin • Progressive loss of basaloid epithelium • Foreign body giant cell reaction to keratin • Calcification, ossification
  • 125. • They resemble the cells of a basal cell carcinoma. They are sometimes the predominant cell in lesions removed from elderly patients. • The term ‘proliferating pilomatricoma’ has been proposed for this variant • Calcification occurs in more than two-thirds of the tumors and is usually in the shadow cells
  • 126. • There are masses of epithelial cells of various shapes, with an intervening connective tissue stroma containing blood vessels, a mixed inflammatory cell infiltrate, foreign body giant cells, and sometimes hemosiderin, melanin, bone, and rarely amyloid.
  • 127. (A) Pilomatricoma. (B) There are two cell types present – nests of basaloid cells and shadow cells. The lesion is partly cystic.
  • 128. Pilomatricoma. Round cystic tumor with basaloid epithelial lining and eosinophilic keratinous contents.
  • 129. Trichoblastoma Clinical Features Adults Women as often as men Almost any location, especially the face and scalp Usually does not involve distal extremities Solitary nondescript papule or nodule Usually <2 cm, but may be giant Histopathologic Features Well demarcated from surrounding tissue Symmetric Basaloid epithelial proliferation in cords, sheets, or discrete clusters Fibrotic investment of epithelium Follicular germinative epithelium
  • 130. • Peripheral palisading of nuclei • Follicular differentiation resembling hair bulbs and papillae • Keratinous cysts on occasion • Fibrotic stroma • Occasional necrosis • Limited numbers of mitoses • Differential Diagnosis • Basal cell carcinoma
  • 131. Trichoblastoma. This basaloid tumor resembles basal cell carcinoma.There is some trichogenic differentiation and stromal induction.
  • 132. This striking simulation of hair matrix and hair papilla by the mesenchymal stroma and basaloid epithelium in hair germinative tumors is referred to as a papillary mesenchymal body.
  • 133. Pigmented trichoblastoma. There is focal stromal induction with the formation of primitive follicular structures.
  • 134. Approach to skin adnexal tumors
  • 135. GENERAL APPROACH TO ADNEXAL TUMORS ADNEXAL TUMORS WITH EPIDERMAL CONNECTION WITH NO EPIDERMAL CONNECTION SEBACEOUS TUMORS CYSTS
  • 136. PREDOMINANTLY WITH EPIDERMAL CONNECTION BASALOID ( BLUE) TUMOR + CUTICLE FORMATION POROMA POROCARCINOMA +CLEAR OR EOSINOPHILIC CYTOPLASM + PERIPHERAL NUCLEAR PALISADING TRICHILEMMOMA + DILATED FOLLICULAR ORIFICE TRICHOFOLLICULOMA DILATED PORE OF WINER PILAR SHEATH ACANTHOMA DUCTS , GLANDS AND PAPILLAE SYRINGOCYSTADENOMA PAPILLIFERUM VACULATED CYTOPLASM SEBACEOUS TUMOR
  • 137. TUMOR WITH NO EPIDERMAL CONNECTION PREDOMINANTLY WITH NO EPIDERMAL CONNECTION BASALOID TUMOR CLEAR CELLS AND EOSINOPHILIC CYTOPLASM +/- CYSTIC CHANGES DUCTAL / GLANDULAR FORMATION
  • 138. PREDOMINANTLY NO EPIDERMAL CONNECTION PERIPHERAL NUCLEAR PALISADING TRICHOEPITHELIOMA TRICHOBLASTOMA TWO CELL TYPES + INTERMINGLED LYOMPHOCYTES SPIRADENOMA CYLINDROMA CUTICLE ( SMALL DUCTS) FORMATION DERMAL DUCT TUMOR GHOST CELLS PILOMATRIXOMA VACOULATED CYTOPLASM SEBACEOMA SEBACEOUS CARCINOMA BASALOID TUMOR EXCLUDE BASAL CELL CARCINOMA
  • 139. PREDOMINANTLY WITH NO EPIDERMAL CONNECTION CLEAR AND EOSINOPHILIC CYTOPLASM +/- CYSTIC CHANGE HIDRADENOMA HIDRADENOCARCINOMA EXCLUDE METABOLIC RENAL CELL ACRCINOMA
  • 140.
  • 141. TUMORS WITH SEBACEOUS DIFFERENTIATION

Editor's Notes

  1. This cross section of anagen phase follicle at the level of isthmus shows central hair shaft This cross section shows telogen phase follicle ( resting phase ) at the level of isthmus
  2. Sebaceous gland associated with a terminal hair follicle Mature sebocytes in the center of the lobule have ample multivacuolated cytoplasm in many cells , the intracytop;asmic vacuoles indent the nucleus imparting a scalloped appearance
  3. The nuclei are round to oval with vesicular to hyperchromatic appearing chromatin
  4. Sebaceous hyperplasia: the hyperplastic sebaceous lobules mirror the normal sebaceous gland and consist of an outer layer of basaloid cells surrounding mature sebaceous cells with eosinophilic bubbly cytoplasm
  5. Pagetoid involvement by neoplastic sebocytes show multivacuolated pale cytoplasm
  6. Mismatch repair protein by IHC A shows MSH -2 AND MSH-6 staining are lost while PMS-2 (B) and MLH-1 (D) staining are retained This pattern of staining compatible with MSH2 gene mutation the most common MMR gene mutation in MUIRE TORRE SYNDROME
  7. Well-circumscribed nests of basaloid cells are present within the epidermis. (
  8. Multiple turban tumors involving the scalp , well circumscribed dermal tumor beneath grenz zone , a mosaic ( jigsaw puzzle ) pattern