Benign epidermal neoplasms Flashcards
What is the underlying pathogenesis of solar lentigines
Epidermal hyperplasia
Variable proliferation of melanocytes
Accumulation of melanin within keratinocytes in response to chronic exposure to UVR
What somatic mutations have been identified in solar lentigines
FGFR3
PIK3CA
What somatic mutations have been identified in PUVA lentigines
BRAF
What mutations have been identified in seb ks
FGFR3 and PIK3CA
Mutations in lichenoid keratosis
FGFR3, PI3KCA
HRA >KRAS
Mutation in dermatosis papulosa nigra
FGFR3
Mutation in stucco keratosis
PIK3CA
Mutation in epidermal naevi
FGFR3, PIK3CA
HRA > NRAS > KRAS
Mutation in acneiform naevus with hypopigmented background skin
FGFR2
Mutation in naevus comedonicus
NEK9
Dermoscopy of solar lentigo
Diffuse light brown structureless area
Sharply demarcated and/or moth eaten borders
fingerprting
reticular pattern with thin lines that are occasionally short and interrupted
Variant: ink spot lentigo - striking jet black colour and a stellate outline, black branching pattern
How are PUVA lentigines clinically, pathologically and genetically different
Darker brown
Stellate appearance
On histo: lentiginous hyperplasia of large melanocytes, mild cytologic atypia
Often contain BRAF mutations
Solar lentigines pathology
Rete ridges: club shaped or bud like extensions
Increased basal layer pigmentation
Melanocytes may be slightly increased in number
DOPA-stained: increased melanogenesis, these cells have more numerous as well as longer and thicker dendritic processes than the melanocytes of normal skin
Superficial dermis: melanophages, occasionally mild peri-vascular lymphocytic infiltrate
Solar elastosis
Pathogenesis of seb ks
Some genetic (Caucasians)
Sun exposure - link to solar lentigines
Genes: FGFR3 and PIK3CA
Pathogenesis of irritated seb ks
Apoptosis within areas of squamous differentation
HPV not really a culprit
Rarely from bacterial infection
What are some features that help differentiate seb ks from melanocytic neoplasms
Keratotic plugging (although you can see in some compound and intradermal melanocytic naevi)
Stuck on appearance
Overlying scale
Conditions associated with abrupt seb k eruption and regression
Pregnancy
Coexisting inflammatory dermatoses
Malignancy: Leser Trelat
What cancers can arise in seb ks, and which is most common
Most common: BCC
Others: SCC, bowens, cutaneous melanoma, KA
What is Leser Trelat associated with?
Malignancy: particularly gastric, colonic adenocarcinoma, breast carcinoma, lymphoma
Can occur before, during or after
40% have associated pruirtus
Majority on back, followed by extremities, face and abdomen
20% have malignancy acanthosis nigricans (may appear at the same time or shortly after the sign of Leser Trelat)
What is the pathogenesis of Leser Trelat?
Thought to be related to secretion of growth factor by the neplasm which leads to epithelial hyperplasia
It has been hotly contested given so many people > age have got seb ks
Histologic types of seb ks
- Acanthotic (most common)
- Hyperkeratotic
- Reticulated
- Irritated
- Clonal
- Melanoacanthoma
(CHAIRM)
Basic seb k histology
Varying degrees of hyperkeratosis, acanthosis and papillomatosis
Key features:
- Horn pseudocysts: cross-sectioned epidermal invaginations
- Acanthosis: result of an accumulation of benign squamous and basaloid keratinocytes - typically projecting outward and upward in an irregular fashion
- String sign: sharp demarcation at the base of most lesions
- Church spires: papillomatosis and hyperkeratosis
- No dermal involvement
Some contain basaloid cells over squamous - smaller, uniform appearance, large oval-shaped nuclei
No atypia
Inflamed seb k histology
Mild keratinocyte atypia
Mitotic figures
Acanthotic seb k histology
Smooth surfaced, dome shaped papule
Slight hyperkeratosis and papillomatosis
Thickened epidermis with ++ basaloid cells
Invaginated horn pseudocysts are most prevalent in this variant
Melanin increased - primarily concentrated in keratinocytes and is transferred from neighbouring melanocytes
Hyperkeratotic seb k histology
Prominent hyperkeratosis and papillomatosis - ‘church spires’
Squamous cells»_space; basaloid cells
Not much pigment
Less pseudocysts
Reticulated or adenoid seb k histology
Delicate strands of epithelium that extend from the epidermis in an interlacing pattern
Double row or more of basaloid cells that may be hyperpigmented
Horn pseudocysts may be present
Solar lentigo often seen at lateral margins
Irritated seb k histology
Lymphoid infiltrate - can be perivascular, diffuse or licehnoid
Spongiosis
Keratinocyte necrosis
Squamous eddies are common - whorls of eosinophilic keratinocytes
Often lack the sharply demarcated horizontal base seen with most seb ks
Clonal seb k histology (aka nested)
Well defined nests of loosely packed cells within the epithelium
Nests are composed of variably sized kerastinocytes that are paler than adjacent cells and have a uniform appearance
May also contain melanocytes
Can have Borst-Jadassohn phenomenon: intraepidermal epithelioma - you see this with eccrine poroma and other intraepidermal sweat glands, Bowens
Melanoacanthoma seb k histology
Seb k that mimics MIS
Negative for Melan-A/MART-1 and S100
What conditions are thought to be variants of seb ks
DPN
Stucco keratosis
Inverted follicular keratoses
Can solar lentigines become seb ks
Yes: over time the buds of pigmented basaloid cells become thicker and there is greater acanthosis
What is a melanoacanthoma?
Heavily pigmented: keratincoytes contain the nulk of pigment (have long dendrites), and there are melanocytes distributed throughout the lesion
The heavy pigmentation is explained by the blockage of transfer of melanin to keratinocytes - resulting in an increase in the amount of melanin within melanocytes
Different to a seb k, is a ddx for melanoacanthoma seb k
Histo: minimal epidermal hyperplasia, look more like a heavily pigmented lentigo simplex with a proliferation of dendritic melanocytes within the basal layer of the epithelium
Seb k ddx
- The variants: DPN, stucco keratosis, inverted follicular keratoses
- Other benign epidermal and melanocytic neoplasms:
- solar lentigo
- acrochordon
- melanocytic naevus
- tumour of the follicular infundibulum - superficial distinct plate-like epithelial proliferation - multiple slender epidermal connections composed of basaloid or pale cells
- eccrine poroma (for acanthotic and iritated –> poromas are homogenous, small basophilic cells with delicate fibrovascular stroma and narrow ductal lumina with eosinophilic, PAS-positive, diastase resistant cuticles)
- melanoacanthoma
- AN
- epidermal naevus
- CARP
- acrokeratosis verruciformis of Hopf
- acanthoma fissuratum (epidermal hyperplasia due to friction) - Malignancies:
- Bowen disease (can have Borst Jadassohn phenomenon)
- SCC
- melanoma (particulary verrucous) - Infectious:
- verruca vulgaris
- condyloma accuminatum
Seb k rx
LN2 C&C/shave Electrodessication Laser: Erb:Yag AKT inhibitors - possible future topical therapy
Pathogenesis of lichenoid keratosis
Inflammation of solar lentigo, ak or seb k
Lichenoid infiltrate of lymphocytes secondary to a stimulus from an unidentified epidermal antigen
Common site for lichenoid keratosis
Forearm and upper chest, less frequent occurrence on shins and other chronically sun exposed sites
Lichenoid keratosis dermoscopy
Light brown pseudonetworks due to residual solar lentigo
Overlapping pinkish areas due to lichenoid inflammation
Annular granular structures and gray pseudonetworks in the early regressing stage
White blue-gray fine dots can be seen in the late regressing stage
Blue-gray dots or globules - representing melanophages - are also considered typical of an LK
Lichenoid keratosis pathology
- Lichenoid change: lymphocytes with scattered histiocytes, +/- eos and plasma cells, full interface dermatitis - basal vacuolar alteration, melanin incontinence, colloid bodies (if ++ melanin incontinence can be called pigmented LK)
- Epidermal changes: can have parakeratosis, can have frank separation of epidermis from the infiltrate in the dermis –> sub-epidermal cleft or blister cavity
- Changes of solar lentigo or macular seb k present at periphery of specimen
- Regression - can undergo, loosely fibrotic papillary dermis with scattered lymphocytes and melanophages. Can be confused for a melanoma, but a regressed melanoma will have a dense band of melanophages with lymphocytes and dilated blood vessels, with thin epidermis
- Mimicks MF (Pautrier like microabscesses, alignment of lymphocytes along the basal layer, epidermotropism) and lupus (atrophic variant)
Naevus comedonicus epidemiology
Half present at birth
Others appear in childhood, usually before age 10
Adulthood is rare and associated with irritation or trauma
What is the underlying pathogenesis of naevus comedonicus
Growth dysregulation affecting the mesodermal portion of the pilosebaceous unit
NEK9 (NIMA related kinase 9 gene) has been identified as mosaic activating mutation
How is a Munro acne naevus different to naevus comedonicus
Has FGFR2 mutation - has pre-existing linear hypopigmentation, peripubertal onset of acne, and histo shows an atrophic comedonal wall with prominent associated sebaceous lobules
Can you get a skin cancer in naevus comedonicus
Yes very rare reports of SCC or KA
Where is naevus comedonicus distributed
Face most commonly, then trunk, neck, upper extremity
Can also occur on palms, soles, glans penis
Elbows and knees: can be verrucous in appearance
Worsens with hormones
What is familial dyskeratotic comedones
Rare autosomal dominant disorder in which comedones arise during childhood or adolescece
Widely scattered to trunk and extremities
No linear configuration
Ddx for naevus comedonicus
Infantile acne Chloracne Familial dyskeratotic comedones Dilated pore naevus Porokeratotic eccrine ostial and dermal duct naevi
CARP associations
Obesity Menstrual irregularities DM Pituitary disorders Thyroid disorders
CARP pathogenesis postulations
- ?Malassezia furfur response
- ?Insulin resistance
- Keratinization disorder
CARP pathology
Hyperkeratosis
Acanthosis
Papillomatosis
Sparse, superficial perivascular infiltrates of lymphocytes
‘Dirty feet’: club-shaped, bulbous epidermal rete ridges that protrude slightly into the papillary dermis with pigment at their bases
CARP ddx
AN
Tinea versicolor
Darier
Retention hyperkeratosis
Histo: seb k, epidermal naevus, AN, papillomatous epithelial proliferation
Clear cell papulosis epidermiology
Chinese and other Asian children
Where does clear cell papulosis appear
Milk lines (mammary ridge)
Clear cell papulosis pathogenesis
? benign extra mammary Paget disease
Clear cells in lesional skin suggests histogenic relationship with Toker cells
Clear cell papulosis clinical
Multiple white macules or papules 2-10 mm in diameter that favour the anterior chest, abdomen and lumbar region, and milk lines
Rarely the face
Clear cell papulosis histology
Mild acanthosis
Slightly disorganized arrangement of epidermal keratinocytes
Numerous clear cells scattered primarily along the basal layer of the epidermis but also within its upper layers
Cells have ++ mucin in their cytoplasm
Stain with PAS, ALcian blue, mucicarmine, colloidal iron
Immunohistochemistry: clear cells express CEA, cytokeratins: CK7, AE1/3, CAM5.2, EMA, gross cystic disease fluid protein
Negative for CD1a, S100 and HMB45
Histologically looks like Paget disease
