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PATHOLOGY of the SKIN - Coggle Diagram
PATHOLOGY of the SKIN
inflammatory disorders
differential diagnosis based on
clinical presentation
anamnestic information
macroscopic images
histology
histochemistry
IHC/IF
immunofluorescence is needed because it gives a more precise subcellular description of the reaction with respect to ICH in the setting of inflammatory reactions
primary epidermal alterations / spongiotic dermatitis
possible clinical forms
allergic contact dermatitis
atopic dermatitis
seborrheic dermatitis
dyshidrotic eczema
spongiotic drug eruption
spongiotic insect bite reaction
common pathological lesion
SPONGIOSIS
pathological process in which the patient has an edema forming vesicles in the epidermis
intraepidermal lesions (acute phase - vesicular eruption --> crust/plaque formation) evolve into hyperkeratotic lesions during the chronic phase
both lesions may be present simultaneously
no living cells are seen in these lesions
consequence of a cell-mediated immune response (type IV - T cells)
acanthotic dermatitis
variable erythematous patch, plaque, papule or nodule
dominant pathological lesion
ACANTHOSIS
hyperplasia of th eintermediate layer of the epidermis
NO HYPERKERATOSIS
no involvement of the superficial layer
two main forms
lichen simplex chronicus
erythematous plaques at the site of rubbing or irritation
in case of itching: PRURIGO NODULARIS
psoriasis
chronic and relapsing disease with erythema, epidermal thickening and scale formation
familial predisposition
frequent nails involvement
skin and joint lesions
DD: chronic eczematous dermatitis
Auspitz sign
minute bleding points from peeling of the surface scale of a plaque
diagnosis based on skin biopsy
primary acantholytic
pathogenesis
AI
drugs
paraneoplastic
thymoma/lymphoproliferative disorder
herpes viruses
histology
ACANTHOLYSIS
blisters with viable cells floating within the blister cavity
DD: blisters in spongiosis
clinical forms
pemphigus vulgaris
rare, but potentially lethal
protein loss and sepsis
skin and oral mucosa
autoimmune
circulating Abs against adhesion proteins of squamous cells
desmoglein 1
desmoglein 3
herpesvirus blisters
negative immunofluorescence
cytopathic nuclear changes
necrosis
neutrophils
(non-acantolythic)
vesciculo-bullous and vesciculo-pustular dermatitis
heterogeneous disorsers, potentially life-threatening
histology
subepidermal fluid-filld cavity formation
clinical forms
bullous pemphigoid
epidermolysis bullosa
dermatitis herpetiform
linear IgA disease
bullous pemphigoid
rare
F>M
40-60 years
oral mucosa, skin, eyes, nasal cavity
IgG, IgA and C3 deposit
linear pattern on the basal membrane
pathogenesis
often autoimmine
Abs against structural proteins integral to the dermal-epidermal stability
interface dermatitis -
acute cytotoxic dermatitis
pathogenesis
autoimmune
drugs
infections
dominant histological features
superficial perivascular and interstitial papillary iniltrate
apposition of lymphocytes along a focally damaged basal cell layer
epidermotropic lymphocytic migration with necrosis/apoptosis
pigment incontinence and dermal fibrosis with basal membrane thickening
clinical forms
erythema multiforme
acute graft-vs-host disease
acute cytotoxic generalized drug eruption
interface dermatitis from HIV
lichenoid dermatitis -
subacute-to-chronic cytotoxic dermatitis
pathognesis
autoimmune
drugs
infections
dominant histological features
abnormal keratinization (dyskeratosis)
cell death
(colloid body formation)
altered cellular maturation
clinical forms
lichen planus
chronic graft-vs-host disease
SLE
dermatomyositis
secondary syphilis
lichen sclerosus
lichen planus
pruritic
pink to purple papules
middle-aged individuals
skin, buccal mucosa, genital skin
acute-to-chronic course
unknown pathogenesis (AI?)
band-like infiltrate of lymphocytes within the papillary dermis, hyperkeratosis, saw-tooth architecture of the rete ridges, colloid (CIVATTE) bodies IgM +, atrophyc variant
lupus erythematosus
systemic AID
heterogeneous presentation in the skin
classic discoid
acute/subacute with subtle histology
bullous
necrotizing
typically epidermal atrophy
prominent periphollicular/perivascular dense infiltrate
in active lesions prominent basal layer vacuolization and apoptosis
inactive lesions with lack of inflammation
thickening of the basal membrane
merkel cell carcinoma
presentation:
rare
increasing incidence (sun exposure and/or increased diagnostic procedures)
more common in elderly (70-80 y) white men (M:F =2:1)
history of extensive sun exposure
head and neck location
also on cutaneous primary locations (LN, mucosa, salivary glands)
macroscopy:
erythematous nodules
rapid growth and ulceration
sometimes associated with scars or other cutaneous neoplasms
pathogenesis
UV exposure
immunosuppression
iatrogenic
lymphoproliferative diseases
HIV
immunosenescence
Merkel cell polyoma virus
60-80% of the general population
integration with the host genome, forming 2 onco-proteins
large T antigen (LT)
small T antigen (ST)
diagnostic workup:
biopsy of skin lesion
architectural patterns of HG-NEC
neuroendocrine differentiation
CK20
CgA
TTF-1
CLA
evaluation of lymph nodes
FNA for clinical positive nodes
sentinel lymph node for clinically negative nodes
1/3 of occult metastases
DD:
melanoma
lymphoid neoplasms
squamous cell carcinoma with basaloid features
PNET/DSRCT
NE markers have a scarce value
MCPolyV has a lower frequency in LN MTS
CK20 not completely established in other NECs
TTF-1 not completely sentitive and specific
staging system
very different from the one of SqCC, but similar to that of melanoma
sentinel lymph node biopsy
parameters:
thickness of the lesion (Breslow system)
type of growth (nodular vs infiltrative)
presence of invasion
mitotic index
tumor infiltrating lymphocytes (TILs)
high TILs:
UV-associated MCC
high immune protection burden
therapy
immunotherapy (anti-PDL1)
neoplasms of the dermis
benign
benign fibrous histiocytoma (dermatofibroma)
xanthoma
borderline
dermatofibrosarcoma protuberans
local recurrence
cytological atypia
irregular margins
CD34+
malignant
Kaposi sarcoma
skin cutaneous
african variant in lymph nodes (children)
AIDS-related
micro
vascular/pseudovascular spaces dissecting dermis
connective tissue with atypical endothelial cells
association with HHV8
hematologic neoplasms
mycosis fungoid
cutaneous T-cell lymphoma
macro:
eczematous lesion
red plaque persistent over years
if hematogenous spread
diffuse erythema
sezary syndrome
micro:
Sezary cells
aggregates of CD4+ T cells
band-like in the dermis
Pautrier abscess in the epidermis
cerebroid nuclei
other T-cell lymphomas
large cell, anaplastic, CD30+
NK lymhoma
T peripheric cutaneous lymphoma, low grade
B-cell lymphomas MALT-type
histiocytosis X
Langherans cells
children
micro:
infiltrate of mononucleated CD1a + cells in the dermis
granules of Birbeck at EM
macro:
diffuse macules
papules
epithelial neoplasms
benign
seborrheic keratitis
basal cell proliferation
intra-epidermic
often pigmentedd
with keratin cysts
elevated/papillomatous
adults/elderly
malignant
non-invasive
actinic keratosis
pre-malignant
UV exposure
elderly
dysplasia
lack of the basal cell stratum
Bowen's disease
squamous cell carcinoma in situ
marked cellular atypia
erythematous plaques (everywhere in the body)
up to 5% will become invasive
erythroplasia of Queyrat
male genitals
keratoacanthoma
forearm/hand
low grade
initial rapid growth followed by a period of variable tumor stability and spontaneous regression
1-2 cm dome-shaped
proliferation of squamous clls with hyperkeratinization with a centralized keratinous plug
invasive
squamous cell carcinoma
frequent in elderly
UV exposure
typical histology with infiltrative growth
variants
acantholytic
verrucous
spindle cell
aggressive locally, to LNs and distant metastases
basal cell carcinoma
UV exposure
proliferation of basaloid cells
in nests with palisading, sometimes pigmented
marked desmoplastic reaction
locally aggressive, no metastases
variants
nodulocystic
superficial
pigmented
morpheaform
infiltrative
baso-squamous
clear cell
familial forms in the setting of the nevoid basal cell carcinoma syndrome
germline PTCH mutations
tumors of the adnexa
benign / malignant
apocrine / eccrine
follicular / sebaceous
very heterogeneous
IHC markers are not that useful
DD
epidermal neoplasms
metastases
melanocytic neoplasms
malignant melanoma
5% skin malignancies
increased incidence
70% of deaths for skin cancer
10% familial (CDKN2A)
85% skin location (de novo or evolutive from nevus)
15% cutaneous (eye, nose, anal canal, meninges)
risk factors:
increased number of nevi
dysplastic nevi
"clear" phenotype
actinic skin damage
familiarity
UV (more exposed areas)
white and clear phenotype
genetics: not relevant because not used for diagnosis making
still, some molecular alterations exist
BRAF
KIT
macro: aspecific, size (>1 cm), irregular borders, asymmetry, heterogeneous pigmentation
micro: radial vs vertical growth
radial
de novo
intra-epidermic growth, then extending into the superficial dermis (no metastatic potential)
nevus-associated
vertical
into the deep dermis
nodular melanoma with metastatic potential
pathological types
superficial spreading melanoma:
UV exposed areas
pigmented or amelanotic
radial growth at the DEJ, then vertical growth
CDK4 and CCND1
nodular melanoma:
early vertical growth
no radial component
often ulcerated
no site predilection
BRAF and NRAS
lentiginous acral melanoma:
palm/plant pf feet/nails, oral, nose, anal mucosa
no UV exposure
marked atypia
lentiginous growth with epidermic hyperplasia and inflammation
c-KIT mutations/amplification
CDK4 and CCND1 amplification
melanoma over lentigo maligna:
melanocytic proliferation in UV exposed areas
elderly
radial growth
single highly atypical melanocytes
when vertical growth occurs: malignant melanoma transformation
c-KIT mutations/amplification
CCND1 amplification
depth of invasion
Clark levels
1- epidermis
2- papillary dermis
3- papillary reticular dermal interface
4- reticular dermis
5- subcutaneous tissue
Breslow thicnkess
specific measurement of the invasion depth, independently of the type of tissue involved
TNM staging
T stage
thickness of the invasion
ulceration state of the patient
N stage
assess the number of lymph nodes that are involved, their location is not takn into account
sentinel lymph node
not specific for melanomas, also seen in breast cancer
it's the first lymph node that drains the specific area of the tumor
marker: methylene blue or radioactive marker
in transit metastases
specific for skin tumors only
irrelevant prognostic indicator
found in any kind of nodal stage
M stage
cutaneous vs non-cutaneous
CNS vs others
relevant pathological features
histology
thickness (Barlow)
Clark levels
ulceration
mitotic index
type of growth
regression
TILs
vascular and perineural invasion
in transit metastasis
pigmentation
resection margins
satellitosis
associated nevus
pTNM
how to assess tumor regression
fibrosis, foamy histiocytes and cholesterol deposits
benign neoplasms
NEVI
congenital (at birth, variable size, giant form, often admixed with adnexa)
acquired (after 1st year, usually within the first two decades, small)
congenital superficial
present at birth, every site, <1,5 cm, deep and uniform infiltrate, band-like structure, along adnexa and angiocentric, junctional component sometimes present
macroscopy highly heterogeneous in terms of colour(light-to-dark brown) and shape (flat-to-dome-shaped)
microscopy: proliferation of melanocytes in nests at the DEJ
junctional nevus
then, extension to the superficial dermis
compound nevus
or full maturation and loss of junctional component
dermal nevus
special types
blue nevus
intensively pigmented
proliferation of pigmented melanocytes in the reticular dermis
size >1 cm
fusiform architecture
heterogeneous cellularity
DD: melanoma
reed nevus
intensively pigmented
rapid onset
young adults
more frequent in the limbs
fusiform mlanocytes
at DEJ
combined nevus
every nevus (congenital or acquired)
two or more histological types
dysplastic nevus
5-10 mm
single, but frequently multiple
metachronous
flat
variable pigmentation
micro: intraepidermic nests of melanocytes, with a tendency to fuse, cytological atypia, lymphoid infiltrate and fibrosis in the dermis
dysplastic nevus syndrome
hereditary
50% will develop melanoma before 59 years of age
spitz nevus
face or legs
first two decades of life
small (<1 cm)
pink papule
hypopigmanted
microscopy:
proliferation of large ovoidal melanocytes, aboundant eosinophilic cytoplasm, multinucleated
epidermal thickeningm isolated nests, Kamino bodies
compounds forms
several variants
"atypical" from