Derm Flashcards
1
Q
70 yo male with cheek mass;
DDx?
Stains?
A
Melanoma: spindle and desmoplastic
- Face is good location
- Spindle cell: Nests of melanocytes
- Desmoplastic: atypical spindle cells in stroma a/w lymphs
- S100, SOX10 (both sensitive)
DFSP
- bland, uniform cells, translocation sarcoma which means uniform
- t(17;22)
Spindle cell variant of SCC
- PanCK or p40/p63
Epitheliod sarcoma
AFX
- confined to dermis
Undifferentiated pleomorphic sarcoma
- subcutaneous
Leiomyosarcoma
- desmin
All neg - afx/mfh depending on depth
2
Q
15 yo female with subcutaneous flank mass.
A
Rosai-Dorfman
- Subcutaneous
- Nodules of histiocytes w blue lymphocyte/plasma cell clusters
- Round histiocytes w vesicular chromatin, prominent nucleoli, abundant cytoplasm
- Pink and blue on low power
- S100 will stain histiocytes
- Aka sinus histiocytosis with massive lymphadenopathy if found in a lymph node
- LCH is more superficial
3
Q
30 yo female with enlarging calf nodule.
A
Dermatofibroma with aneurysmal change
- Acanthosis w tabling of rete, entrapped collagen in the periphery, blood filled spaces, hemosiderin, foamy cells, tuton giant cells
DDx
Vascular tumor
- CD31 - good for dermal vascular stain BUT histiocytes will stain granular positive
- Erg - better marker, nuclear marker
4
Q
30 yo male with ankle mass.
A
Chondroid Syringoma
- mixed tumor
- similar to pleomorphic adenoma in salivary gland
- tyrosine crystaloids
- myoepithelial cells stain with CK and S100
- chordoma stains with brachyurea, CK, S100
5
Q
9 yo female with forehead mass.
A
Glomus Tumor
- monotonous cells with basement membrane material (collagen IV) surrounding individual cells
- edge of mass: glomus cells trickling along vessels
- myoid not vascular cells
- stain with actin
6
Q
50 yo female with scalp mass.
A
Epithelioid Hemangioendothelioma
- myxoid background
- epithelioid cells in chains or nests
- blister cells trying to make vascular channels but can’t
- translocation WWTR1-CAMTA1, YAP1-TFE3 fusion gene
7
Q
A
LICHEN PLANUS (LP)
- band-like infiltrate
- acanthosis
- jagged rete ridges
- hypergranulosis
- squamatization
- colloid bodies
8
Q
LP DDx
A
Differential Diagnosis
- eosinophils –> lichenoid drug reaction
- plasma cells –> secondary syphilis
- Single lesion with pigment incontinence (common on chest, biceps) –> lichen planus-like keratosis
- Many necrotic keratinocytics (full thickness), less inflammation –> erythema multiforme (EM)
- Look for eosinophils and pigment incontinence = fixed drug eruption
9
Q
A
ERYTHEMA MULTIFORME (EM) & TOXIC EPIDERMAL NECROLYSIS (TEN)
& SJS
10
Q
Definition?
Associations?
A
ERYTHEMA MULTIFORME (EM) & TOXIC EPIDERMAL NECROLYSIS (TEN)
- EM: lichenoid dermatitis with necrotic keratinocytes (civatte bodies) prominent or confluent (full thickness)
- a/w infections: HSV, mycoplasma
- Steven’s Johnson Syndrome: identical histology to EM or TEN + mucosal involvement
- a/w drugs: sulfonamides, NSAIDs
- TEN: full thickness epidermal necrosis + > 30% surface involvement
- progression of SJS or de novo
11
Q
A
ACUTE GRAFT-VERSUS-HOST DISEASE (GVHD)
- EM-like with vacuolar change
- dyskeratotic cells
- periadnexal infiltrates
- no/few eos (but presence does not rule out the dx)
12
Q
Grading GVHD
A
Grading GVHD
- Grade 0: No changes
- Grade 1: Mild/focal basal vacuolar change (DRUG)
- Grade 2: Increased vacuolar change with scattered dyskeratotic cells
- Grade 3: Confluence of basal vacuoles forming subepidermal split, with increased dyskeratotic cells (EM)
- Grade 4: Complete necrosis/loss of epidermis (TEN)
13
Q
DDx?
Tests?
A
Lupus Erythematosus
Discoid LE (DLE):
- epidermal atrophy
- interface, superficial and deep perivascular & periadnexal infiltrate of lymphocytes with plasma cells
- dermal mucin (highlight with Alcian blue or colloidal Fe)
- BM thickening
Subacute cutaneous LE (SCLE) and systemic LE (SLE):
- similar to DLE, but milder infiltrate
- more vacuolar change
- apoptotic cells more prominent in SCLE
- serology
DIF:
- positive “lupus band test”
- deposition of IgG, IgA, IgM, ± C3 along basement membrane
14
Q
A
DERMATOMYOSITIS (DM)
- Histologic findings similar to SLE, but often milder
- epidermal atrophy
- less infiltrates
- no deep or periadnexal infiltrates
- less mucin
15
Q
A
LICHEN NITIDUS (LN)
- small papillary dermal collections of lymphocytes
- “ball in claw” pattern
- focal granulomatous appearance (not true granulomas)
16
Q
A
LICHEN SCLEROSUS ET ATROPICUS (LS&A)
- atrophy
- papillary dermal edema
- collagen sclerosis
- follicular plugging
- DDx: radiation dermatitis (perivascular hyalinization, radiation fibroblasts)
17
Q
Dx?
DDx?
A
PITYRIASIS LICHENOIDES ET VARIOLIFORMIS ACUTA (PLEVA) AND CHRONICA (PLC)
PLEVA:
- crusting
- confluent parakeratosis
- dense, wedge-shaped infiltrate
- RBC extravasation
- exocytosis
- scattered dyskeratotic cells
PLC:
- more mild interface changes
- few dyskeratotic cells
- pigment incontinence
DDx: LyP, mf, HSV, drug reaction
18
Q
A
MYCOSIS FUNGOIDES (MF)
- epidermotropism
- Cytologic atypia
- Pautrier’s microabscesses
- CD4+, CD8-, CD7- , CD5+/-, CD30-
19
Q
Histology?
Characteristic of?
A
SPONGIOTIC DERMATITIS +/- EOS
Histology:
- spongiosis +/- eosinophils present in dermis ± epidermis
- occasional vesicles
- parakeratosis and acanthosis in subacute to chronic lesions
Characteristic of:
- allergic contact dermatitis
- atopic dermatitis
- nummular eczema
- hypersensitivity/id reactions
- some drug eruptions
20
Q
A
ALLERGIC CONTACT DERMATITIS
- Inflammatory disorder initiated by contact with an allergen to which to person has been previously sensitized
- Erythematous papules
- small vesicles, or weeping plaques
- usually pruritic
- Usually occurs 12-48 hrs after exposure to allergen (delayed hypersensitivity reaction)
21
Q
DDx for spongiotic dermatitis + distinguishing features
A
DDx for spongiotic dermatitis also includes:
- Dermatophyte infection (Do PAS)
- Scabies (Do levels)
- Arthropod bite reaction (Deep inflammation with many eosinophils)
- Pityriasis rosea (mild sponge with mounds of parakeratosis)
- Seborrheic dermatitis (mounds of para at follicle)
- Vesicular stage of incontinentia pigmenti (pediatric patients)
- Urticarial/spongiotic stage of bullous pemphigoid (many eosinophils)
22
Q
A
DERMATOPHYTOSIS (TINEA)
- Spongiosis +/- eosinophils
- Parakeratosis containing neutrophilic dust
- “Sandwich sign”: hyphae sandwiched between basketweave orthokeratosis above and compact hyperkeratosis or parakeratosis below
23
Q
A
ERYTHEMA MULTIFORME (EM) & TOXIC EPIDERMAL NECROLYSIS (TEN)
& SJS
24
Q
Dx?
Histology?
DDx?
A
PITYRIASIS ROSEA (PR)
- herald patch on torso
- focal mounds of parakeratosis
- underlying spongiosis
- lymphocytes
- RBC extravasation
DDx:
- mild dermatitis
- seborrheic derm (face and scalp, perifollicular parakeratosis)
- pityriasis lichenoides (less sponge, more interface)
- guttate psoriasis (neuts in the scale)
25
Q
A
INCONTINENTIA PIGMENTI (IP), VESICULAR STAGE
- X-linked dominant
- male lethal
- rarely occur in males with Klinefelter (XXY) or somatic mosaicism
- mutations in the NEMO/IKK -gamma gene, chromosome Xq28, regulatory subunit of the inhibitor kappa kinase (IKK) complex and is required for the activation of the transcription factor NF-kappaB (NF-kB). NF-kB is central to many immune, inflammatory, and apoptotic pathways.
- neurocutaneous syndrome with cutaneous, neurologic, ophthalmologic, and dental manifestations (ectoderm and neuroectoderm )
- early, vesicular and/or verrucous stages of incontinentia pigmenti are present at birth or develop in the first few weeks of life i
- Eosinophilic spongiosis w/dyskeratotc keratinocytes
DDx:
- eczematous derm
- erythema toxicum neonatorum (no dyskeratosis)
26
Q
A
NEUTROPHILIC SPONGIOSIS
Found in:
- pustular psoriasis
- subcorneal pustulosis (Sneddon Wilkinson)
- acute generalized exanthematous pustulosis (AGEP)
- dermatophytosis
- bacterial infections
- Reiter’s syndrome
27
Q
Clinical?
A
PSORIASIS
- Common chronic inflammatory dermatosis
- most frequently affects the elbows, knees, scalp, lumbosacral areas, intergluteal cleft, and glans penis
- Well-demarcated, pink to salmon-colored plaque covered by loosely adherent scales that are silver-white in color
- nail changes in 30% of cases
28
Q
Histpathology of psoriasis
A
Histpathology of psoriasis
Regular acanthosis, hypogranulosis, wafer-like parakeratosis with neutrophils, increased pap dermal capillaries (thinning of supra-papillary plates) • Guttate and early psoriasis exhibit less acanthosis and more spongiosis • DDx: clear cell acanthoma (discrete pale zones), chronic spongiotic dermatitis, PRP, LSC, MF
29
Q
A
CHRONIC SPONGIOTIC DERMATITIS
- Irregular or uneven hyperplasia, w/parakeratosis
- spongiosis may be minimal
- no loss of the granular layer
- Any spongiotic dermatitis in chronic phase, including tinea!
30
Q
A
LICHEN SIMPLEX CHRONICUS (LSC) AND PRURIGO NODULARIS
- hyperkeratosis
- irregular acanthosis
- hypergranulosis
- papillary dermal fibrosis
- chronic inflam (+/- eos)
31
Q
MYCOSIS FUNGOIDES, PLAQUE STAGE
A
MYCOSIS FUNGOIDES, PLAQUE STAGE
- Psoriasiform lichenoid pattern
- look for cytologic atypia, epidermotropism, Pautrier’s
32
Q
Syndrome?
Location?
Histology?
DDx?
A
NECROLYTIC MIGRATORY ERYTHEMA (NME)
- a/w glucagonoma syndrome
- glucagon-secreting tumor
- diabetes mellitus
- hypoaminoacidemia
- cheilosis
- anemia
- venous thrombosis
- weight loss
- neuropsychiatric features
- genital, anal, buttocks, groin, lower legs
- Histology
- Pale keratinocytes
- superficial necrosis
- neutrophilic crust
DDx:
- zinc (acrodermatitis enteropathica) or niacin (pellagra) deficiency
- psoriasis
33
Q
Vesiculobullous Reaction Pattern
A
Vesiculobullous Reaction Pattern
- Vesicles or bullae at any level of epidermis
- DIF VERY helpful
- Diagnosis depends on assessment of three features:
- Anatomic level of Split
- Underlying mechanism responsible for split
- Nature of inflammatory infiltrate
34
Q
Clinical?
Histology?
Test?
A
BULLOUS PEMPHIGOID (BP)
- Clin: common, typically older pts. with itchy, tense vesicles/ bullae on flexor surfaces
- Lots of eosinophils in papillary dermis and along DE jn
- DIF: linear basement membrane deposition of IgG, C3
35
Q
Clinical?
Histology?
Test?
A
DERMATITIS HERPETIFORMIS
- Clin: young adult pts, h/o celiac disease; grouped vesicles on extensor surfaces
- Neutrophils ± eos in dermal papillae, ± subepi split
- DIF: papillary dermal deposition of IgA •
- DDx: linear IgA (need DIF to distinguish)
36
Q
Clinical?
Histology?
Test?
A
EPIDERMOLYSIS BULLOSA ACQUISITA (EBA)
Clin: adults, a/w/autoimmune diseases; noninflammatory bullae, extensor surfaces
Histo: pauci-inflammatory blister with few lymphs; rare inflam bullae with neuts, few eos
DIF: thick band of IgG, and to a lesser extent C3, deposited linearly at the basement membrane, +/- IgM or IgA
37
Q
Clinical?
Histology?
Test?
A
PORPHYRIA CUTANEA TARDA (PCT)
- Acral site
- cell-poor blister shows “festooning” (dermal papillae preserved)
- caterpillar bodies adherent to epidermis
- roof of blister has eosinophilic, PAS-D+linear globules
- DIF:
- IgG; to lesser extent IgM, fibrinogen and C3, outline donut–shaped blood vessels in the papillary dermis
- Immunoreactivity also at the dermo-epidermal junction and within basement membrane region of eccrine sweat glands and duct
38
Q
Clinical?
Histology?
Test?
DDx?
A
PEMPHIGUS VULGARIS (PV)
- Flacid, easily ruptured blisters. Oral involvement.
- Suprabasilar acantholysis with “tombstoning” of remaining basal keratinocytes
- Direct immunofluorescence (DIF): intercellular IgG and C3 (fishnet stockings)
- DDx: Darier’s, Grover’s disease, fixation artifact in oral mucosa
39
Q
Clinical?
Histology?
Test?
DDx?
A
PEMPHIGUS FOLIACEUS (PF)
- Superficial bullae usually start on the trunk
- Cleavage at granular layer: beware of the missing stratum corneum
- DIF: mainly IgG4 directed against a cell adhesion molecule, desmoglein 1 (160 kd), expressed mainly in the granular layer of the epidermis.
- DDx: Staph scalded skin syndrome
40
Q
Clinical?
Histology?
Genetics?
Tx?
A
DARIER’S DISEASE
- Clin: autosomal dominant disease, greasy papules on head and neck
- Acanthosis, suprabasal acantholytic dyskeratosis with “corps ronds” (dyskeratotic cells) and grains (parakeratotic cells)
- Mutations in the gene ATP2A2, located on 12q23-24.1, encodes the sarcoplasmic/endoplasmic reticulum Ca2+ -ATP isoform 2 protein (SERCA2)
- This pump maintains a low cytoplasmic Ca2+ level by actively transporting calcium ions from the cytosol into the lumen of the endoplasmic reticulum.
- Miglustat: orphan drug, α-glucosidase inhibitor, restores mature adherens junctions and desmosomes and increases adhesion strength
41
Q
Clinical: itchy lesion on trunk of older white male
Histology?
DDx?
A
TRANSIENT ACANTHOLYTIC DERMATOSIS (GROVER’S)
- Usually trunk of older males, itchy lesions
- 3 patterns may be apparent:
- Spongiotic
- PV or Darier’s-like suprabasilar acantholysis
- Hailey-Hailey-like full thickness acantholysis
- DDX: PV, Darier’s and HHD (clin history), focal acantholytic dyskeratosis (incidental or a/w/underlying lesion, e.g., nevus, scar, etc.)
42
Q
Clinical?
Histology?
Genetics?
Tests?
A
HAILEY-HAILEY DISEASE (BENIGN FAMILIAL PEMPHIGUS)
- Vesicles and erythematous plaques with overlying crusts typically occur in the genital area, as well as the chest, neck, and axillary
- “dilapidated brick wall” with full-thickness and suprabasilar acantholysis
- Defect in a calcium pump protein, ATP2C1 which encodes the secretory pathway Ca2+/Mn2 ATPase (hSPCA1).
- loss of sensitivity to Ca2+ and Mn2+ion binding and transport
- low levels of Ca2+ within Golgi bodies impair protein processing
- DIF is negative
43
Q
Granulomatous Reaction Pattern
5 types?
A
Granulomatous Reaction Pattern
- Presence of chronic granulomatous inflammation
- Five types
- Sarcoidal
- Tuberculoid
- Necrobiotic (collagenolytic) granulomas
- Suppurative
- Foreign body
44
Q
Clinical?
Histology?
DDx?
A
GRANULOMA ANNULARE (GA)
- Dermal papules and annular plaques, young females
- Histology
- Palisaded histiocytes surrounding foci of necrobiosis (degenerative collagen)
- few neuts or eos may be seen
- mucin present
- deep and interstitial forms described
- DDx: NLD (broad, parallel layers of necrobiosis), epithelioid sarcoma (necrosis, atypical cells)
45
Q
A
NECROBIOSIS LIPOIDICA DIABETICORUM (NLD)
- Broad, palisaded layers (“lasagna-like”) of necrobiosis
- Not as discrete as GA, lacks mucin
- All of the dermis all of the time
46
Q
A
RHEUMATOID NODULE
- Deep dermal or SQ nodule
- palisaded histiocytes w/ fibrin in center
- lymphs and plasma cells
- Difficult to tell from deep GA (mucin helpful)
47
Q
A
SARCOIDOSIS
- “Naked” granulomas with scattered lymphocytes, lack necrosis, may see asteroid or Schaumann bodies
- Clinical essential to rule out sarcoid, always mention sarcoidosis in differential diagnos
48
Q
A
TUBERCULOSIS & ATYPICAL MYCOBACTERIAL INFECTIONS
- numerous lymphocytes surrounding granulomas
- abundant histiocytes
- may have neutrophils, esp. early lesions
- often central necrosis
- AFB, Fite stains, cultures required
49
Q
A
FOREIGN BODY REACTION
- Look for “holy” pattern (paraffin, silicone) or ruptured hair follicle/cyst material
50
Q
A
Leukocytoclastic Vasculitis
51
Q
A
Urticaria
- dermal edema
- dilated lymphovascular spaces
52
Q
A
NEUTROPHILIC DERMATOSIS (SWEET’S SYNDROME)
- sudden onset of fever
- elevated white blood cell count
- tender, red, well-demarcated papules and plaques
- dense dermal neutrophilic infiltrate
- NO leukocytoclastic vasculitis
53
Q
Overview of classification of inflammatory skin diseases
A
Overview of classification of inflammatory skin diseases
- A. Lichenoid dermatitis
- B. Spongiotic dermatitis
- C. Psoriasiform dermatitis
- D. Vesiculobullous dermatitis
- E. Granulomatous dermatitis
- F. Vasculopathic dermatitis
- G. Infectious Disease
- H. Panniculitis
- I. Alopecia
54
Q
Lichenoid Dermatitis (9)
A
Lichenoid Dermatitis
- LICHEN PLANUS (LP)
- ERYTHEMA MULTIFORME (EM) & TOXIC EPIDERMAL NECROLYSIS (TEN)
- ACUTE GRAFT-VERSUS-HOST DISEASE (GVHD)
- LUPUS ERYTHEMATOSUS (LE)
- DERMATOMYOSITIS (DM)
- LICHEN NITIDUS
- LICHEN SCLEROSUS ET ATROPICUS (LS&A)
- PITYRIASIS LICHENOIDES ET VARIOLIFORMIS ACUTA (PLEVA) AND CHRONICA (PLC)
- MYCOSIS FUNGOIDES
55
Q
Spongiotic Dermatitis (5)
A
Spongiotic Dermatitis
- SPONGIOTIC DERMATITIS +/- EOSINOPHILS
- DERMATOPHYTOSIS (TINEA)
- PITYRIASIS ROSEA (PR)
- INCONTINENTIA PIGMENTI (IP), VESICULAR STAGE
- NEUTROPHILIC SPONGIOSIS
56
Q
Psoriasiform Dermatitis (5)
A
Psoriasiform Dermatitis
- PSORIASIS
- CHRONIC SPONGIOTIC DERMATITIS
- LICHEN SIMPLEX CHRONICUS (LSC) AND PRURIGO NODULARIS
- MYCOSIS FUNGOIDES, PLAQUE STAGE
- NECROLYTIC MIGRATORY ERYTHEMA (NME)
57
Q
Vesiculo- Bullous Dermatitis
SUBEPIDERMAL (4)
INTRAEPIDERMAL (2)
ACANTHOLYTIC DYSKERATOSIS (3)
A
Vesiculo- Bullous Dermatitis
SUBEPIDERMAL
- BULLOUS PEMPHIGOID (BP)
- DERMATITIS HERPETIFORMIS
- EPIDERMOLYSIS BULLOSA ACQUISITA (EBA)
- PORPHYRIA CUTANEA TARDA (PCT)
INTRAEPIDERMAL
- PEMPHIGUS VULGARIS (PV)
- PEMPHIGUS FOLIACEUS (PF)
ACANTHOLYTIC DYSKERATOSIS
- DARIER’S DISEASE
- TRANSIENT ACANTHOLYTIC DERMATOSIS (GROVER’S)
- HAILEY-HAILEY DISEASE (BENIGN FAMILIAL PEMPHIGUS)
58
Q
Granulomatous Dermatitis (6)
A
Granulomatous Dermatitis
- GRANULOMA ANNULARE (GA)
- NECROBIOSIS LIPOIDICA DIABETICORUM (NLD)
- RHEUMATOID NODULE
- SARCOIDOSIS
- TUBERCULOSIS & ATYPICAL MYCOBACTERIAL INFECTIONS
- FOREIGN BODY REACTION
59
Q
Vasculopathic Dermatitis (3)
A
Vasculopathic Dermatitis
- Leukocytoclastic Vasculitis
- Urticaria
- NEUTROPHILIC DERMATOSIS (SWEET’S SYNDROME)
61
Q
A
STAPH. SCALDED SKIN SYNDROME
- Cell-poor bullae (no organisms)
- very superficial cleavage within or just below granular layer (like pemphigus foliaceus)
62
Q
A
HSV/VZV
- Ballooned and multinucleated keratinocytes with peripheral margination of chromatin
- “steel gray” nucleus
- often epidermal ± follicular necrosis
63
Q
A
MOLLUSCUM CONTAGIOSUM
- Molluscum bodies (eosinophilic intracytoplasmic inclusions)
- caused by poxvirus
64
Q
A
VERRUCA VULGARIS (VV)
- Verrucous epidermal hyperplasia
- HK and PK
- stratum corneum hemorrhage
- prominent keratohyaline granules
- HPV cytopathic changes?
- DDx: verrucous SK, atypical squamous proliferation, verrucous SCC
65
Q
A
DERMATOPHYTOSIS (TINEA)
- Spongiosis +/- eosinophils
- Parakeratosis containing neutrophilic dust
- “Sandwich sign”: hyphae sandwiched between basketweave orthokeratosis above and compact hyperkeratosis or parakeratosis below
66
Q
A
TINEA VERSICOLOR
- Tinea versicolor presents as macules and patches of hypo/hyperpigmentation on trunk.
- Hyphae and yeast forms can be seen on H&E
67
Q
A
CANDIDIASIS
- Yeast and septate pseudohyphae (no branching)
- mucosal surfaces and intertriginous zones
68
Q
A
CHROMOBLASTOMYCOSIS (A.K.A., CHROMOMYCOSIS)
- Medlar bodies
- pigmented yeast forms
- resemble “copper pennies”
69
Q
A
CRYPTOCOCCUS NEOFORMANS
- Large, intracellular or free yeast-like organisms
- mucin stains thick capsule
70
Q
A
HISTOPLASMA CAPSULATUM
- Small intracytoplasmic organisms with surrounding clear halo
- PAS & GMS+
- DDx: leishmaniasis (kinetoplast, Giemsa+)
71
Q
A
LEISHMANIASIS
- Tiny intracytoplasmic organisms
- eccentrically located basophilic kinetoplast
- lack capsule
- Giemsa+
72
Q
A
SCABIES
- Spong derm with prominent dermal eosinophils
- may see intracorneal burrow with mite
73
Q
A
Bullous Impetigo
- Honey Colored Crusts
- Subcorneal blister with neutrophils and bacteria present
- Microbiology Correlation: Gram stain of the blister contents shows gram positive cocci in clusters
75
Q
A
ERYTHEMA NODOSUM (EN)
- Septal pattern of panniculitis
- Miescher’s radial granulomas
- essentially normal epidermis and dermis
- Most common on front of legs
- May be associated with
- drugs (sulfa or NSAID or OCPs)
- infections (TB)
- idiopathic
76
Q
A
ERYTHEMA INDURATUM- NODULAR VASCULITIS
- Classified as a lobular panniculitis
- 30-80% have mycobacterial DNA by PCR
- Histology:
- Septo-lobular panniculitis
- granulomatous inflammation
- vasculitis
- focal necrosis
- DDx: polyarteritis nodosa (more localized)
77
Q
A
PANCREATIC FAT NECROSIS
- Clinical hx important
- Lobular necrosis with abundant neutrophils, presence of calcification
78
Q
A
LIPODERMATOSCLEROSIS (SCLEROSING PANNICULITIS)
- septal and lobular
- lipomembranous fat necrosis
- cystic degeneration
- seen w/stasis dermatitis
79
Q
A
DDX FOR NEEDLE-SHAPED CLEFTS IN THE FAT
- Sclerema neonatorum (lipocytes, min inflammation)
- Subcutaneous fat necrosis of the newborn (lipocytes and giant cells/ inflammation)
- Post-steroid panniculitis (clinical hx)
80
Q
A
Lupus profundus
82
Q
A
ALOPECIA AREATA
- “Swarm of bees”: lymphocytes surrounding anagen hair bulbs
- May only be present in acute/subacute phase
83
Q
A
TRICHOTILLOMANIA
- Trichomalacia (damaged or distorted follicles)
- may see follicular hemorrhage, pigment casts
84
Q
A
LICHEN PLANOPILARIS (LPP)
- Alopecia secondary to inflammatory destruction of follicles
- may see characteristic LP changes
- interface inflammation with dyskeratotic cells
- usually superficial portions of follicles
- Diff dx:
- Lupus-associated alopecia: superficial and deep perivascular and periadnexal infiltrate, ↑’d dermal mucin, BM thickening, DIF+
85
Q
A
SCARRING ALOPECIA
- Often nonspecific, end-stage finding in many different (including inflammatory) causes of alopecia
- Specific entities include:
- central centrifugal scarring alopecia (pseudopelade folliculitis decalvans)
- dissecting cellulitis
- acne keloidalis
- chronic traction
87
Q
- Prognosis?
- Location?
- Age?
- Clinical presentation?
- Frequency of recurrence?
- Cell of origin?
- Genetics?
- Most helpful diagnostic marker? caveat?
- Best way to detect mutation?
DDx:
A
Dermatofibrosarcoma Protuberans
- slow-growing dermal spindle cell tumor of intermediate malignancy
- typically occurs on the trunk and proximal extremities of young and middle-aged adults
- solitary lesion or multiple polypoid nodules arising in an indurated plaque
- Local recurrence is common, occurring in one third of all cases.
- immunohistochemical and ultrastructural evidence indicates a fibroblastic origin
- t(17;22) translocation in > 90% –> pathogenic COL1A1-PDGFB fusion gene
- most helpful diagnostic marker is CD34, which stains 50% to 100% of the cells
- CD34 is negative or focally positive in dermatofibromas
- PCR may be used to identify the COL1A1-PDGFB fusion gene
DDx:
Giant cell fibroblastoma
- considered a variant of dermatofibrosarcoma protuberans that often manifests in childhood
- may exhibit the same immunogenetic and cytogenetic profile as DFSP
Fibrosarcomatous change in DFSP
- characterized by a fascicular or herringbone growth pattern, represents malignant transformation
- fibrosarcomatous areas express CD34 in less than 50% of cases
88
Q
Stains?
EM?
Mutation?
Acute disseminated form?
2 other types?
A
Langerhans Cell Histiocytosis
- Langerhans cell histiocytosis previously was divided into multiple clinical subtypes, but there is much overlap. The different forms of Langerhans cell histiocytosis have similar pathology in that there is a proliferation of Langerhans cells, which can be identified by the distinctive reniform, or kidney-shaped, nuclei.
- Langerhans cells stain positively with S-100 protein and CD1a immunohistochemical stains. Langerhans cells do not stain with CD68.
- With electron microscopy, characteristic Birbeck granules are seen within Langerhans cells. The Birbeck granules resemble a tennis racquet.
- BRAF V600Emutation
Letterer-Siwe disease
- acute disseminated form of Langerhans cell histiocytosis
- usually seen in infants and has many systemic manifestations
- skin lesions are characterized by hyperpigmented scaly patches, which can coalesce and form a seborrheic dermatitis–like eruption
- unresponsive dermatitis in the diaper area
- hyperpigmented papules with associated hemorrhage at the periphery of the dermatitis area
Hand-Schüller-Christian disease
- a form of Langerhans cell histiocytosis that is characterized by the triad of bone lesions, exophthalmos, and diabetes insipidus
Eosinophilic granuloma
- a form of Langerhans cell histiocytosis that usually consists of either a few lesions or one lesion and most commonly affects the bone
- skin and oral mucosa occasionally can be involved.
Congenital self-healing reticulohistiocytosis
- also known as Hashimoto-Pritzker disease
- a variant of Langerhans cell histiocytosis with a very good prognosis
- lesions are often present at birth but can manifest within the first few weeks of life as well
- most commonly, there are scattered papules and nodules over the skin
- occasionally, only a single lesion is present
89
Q
Tuberous sclerosis cutaneous lesions
A
Tuberous sclerosis cutaneous lesions
- hypomelanic macules (ash-leaf)
- facial angiofibromas
- periungal or subungal fibromas
- shagreen patches
- fibrous hamartomas
Two different genes are associated with tuberous sclerosis:
- TSC1 gene: hamartin, 9q34
- TSC2 gene: tuberin, 16p13.3
90
Q
A
Lichen Amyloidosis
- Amyloidosis refers to a group of disorders characterized by abnormal extracellular deposition of β-pleated amyloid protein, either systemically or localized to a specific organ. There are approximately 25 distinct forms of amyloid fibril proteins.
- Primary localized cutaneous amyloidosis is associated with the deposition of amyloid in the skin without associated deposits in internal organs. The most common variants are macular amyloidosis and lichen amyloidosis.
- The amyloid in macular amyloidosis and lichen amyloidosis is believed to be keratinocyte-derived. This belief has been supported by ultrastructural studies demonstrating transitional forms between viable keratinocytes and amyloid and by positive reactions with monoclonal antibodies directed against keratin.
- Lichen amyloidosis usually manifests as persistent, pruritic plaques on the shins or other extensor surfaces of the extremities, particularly the anterior thighs or forearms. Macular amyloidosis manifests as pruritic, hyperpigmented macules that form a rippled pattern, most commonly on the upper back.
- On histopathologic examination, macular amyloidosis and lichen amyloidosis demonstrate amorphous, eosinophilic deposits of amyloid limited to the papillary dermis. Pigment incontinence within melanophages and a sparse perivascular lymphohistiocytic infiltrate are often seen. In lichen amyloidosis, the deposits may expand the papillae and displace the elongated rete ridges laterally. The overlying epidermis is acanthotic and hyperkeratotic.
- Congo red stains amyloid protein a brick-red color, and amyloid exhibits positive “apple-green” birefringence under polarized light. Other histochemical stains that can be used to detect amyloid deposits include crystal violet, methyl violet, PAS, Sirius red, pagoda red, and thioflavine T.
91
Q
aka?
Presentation?
Location?
Time?
Age?
Histology?
DDx?
A
Pernio
- aka chilblains
- inflammatory skin condition
- pruritic, painful, or pruritic and painful violaceous papules and nodules that occur on acral surfaces, most commonly the dorsum of the fingers and toes, but the nose, ears, and thighs also can be affected
- A clue to the diagnosis is the anatomic distribution and cyclic nature of the lesions
- develops in patients exposed to nonfreezing cold in damp conditions
- lesions develop with a change of weather going into winter and resolve during spring and summer
- most commonly, occurs in young women
- Histology
- superficial and deep perivascular land periadnexal ymphocytic dermal inflammatory infiltrates t
- perieccrine accentuation of the infiltrate is characteristic
- varying amount of interface change can be seen
- Pernio and chilblains lupus erythematosus have overlapping clinical and histologic features, evaluate for SLE
- should not be confused with lupus pernio, which refers to a form of cutaneous sarcoidosis
92
Q
Age?
Gender?
Location?
Presentation (early and late)?
Prognosis?
Tx?
What reduces recurrence?
Gross?
Histology?
Stain?
What counts as fibrosarcomatous transformation?
Most common site of dissemination?
Mutation?
A
Dermatofibrosarcoma protuberans
- young adults
- male predominance
- trunk and the proximal extremities
- early lesions have a plaquelike appearance and late lesions are multinodular with skin ulceration
- low-grade sarcoma with a high propensity for local recurrence if incompletely excised
- complete excision requires wide margins because of infiltration beyond the grossly visible margins
- recurrence rate of 20% within 2 years of surgery
- Mohs surgery significantly reduces the rate of recurrence (
- Gross: the lesion is firm and fibrous and varies from a small dermis based plaquelike area or nodule to a large multinodular lesion that ulcerates the overlying skin and deeply involves the underlying adipose tissue
- occasionally may be purely subcutaneous
- Histology:
- proliferation of uniform, mildly atypical spindle cells, arranged in a tight, repetitive storiform pattern
- infiltrates the dermis surrounding the epidermal appendages and infiltrates the fat in a checkerboard or beaded pattern
- lesional cells are uniformly CD34 positive
- may contain fascicular areas that are indistinguishable from fibrosarcoma
- composed of intersecting fascicles of spindle cells with increased atypia and mitotic activity (>10 mitoses per 10 HPFs)
- to be considered fibrosarcomatous, must represent > 5% of the entire lesion
- DFSP with fibrosarcomatous transformation has a small but definite metastatic potential 5% to 10%
- lung is the most common site of dissemination
- t(17;22) COL1A1-PDGFB
94
Q
Presentation?
Age?
Location?
Radiology?
Tx?
Prognosis?
A
Reparative Granuloma (Formerly Giant Cell Reparative Granuloma)
- benign, reactive lesion of bone of unknown cause
- 10 to 25 years
- predilection for facial bones such as the mandible and maxilla
- second most common site is the bones of the hands and feet
- local swelling secondary to the expansion of the contour of the underlying bone
- Xray:
- round or oval lucency with fine trabeculations and well-defined margins
- may expand the contours of the bone and cause cortical thinning
- usually no cortical destruction or periosteal new bone formation
- surgical curettage is the treatment of choice
- recurrence rate is high (33% to 50%) in the lesions of the hands and feet
- in these locations, reparative granulomas that show destructive behavior are best treated by amputation or ray resection
95
Q
Where are the lesions?
What are the antibodies agains?
Tests?
A
Pemphigus Vulgaris
autoimmune blistering disorder
autoantibodies directed against desmoglein 3 and desmoglein 1, desmosomal proteins that are part of the cadherin family
flaccid blisters can develop both in the oral mucosa and on the skin
lesions tend to appear in the oral cavity and proceed to involve the skin
blisters commonly break and leave erosions on the skin
Histology:
- intraepidermal blister, acantholysis and “tombstone” pattern of basal layer keratinocytes
Direct immunofluorescence testing
- perilesional skin adjacent to a blister, distinct pattern of intercellular deposition of IgG and C3 (vulgar fishnet stockings)
Indirect immunofluorescence
- testing a patient’s serum on monkey esophagus, pemphigus vulgaris has a distinct pattern of intercellular deposition of IgG.
ELISA testing can be employed as an additional technique to evaluate a patient’s serum for the presence of antibodies to desmoglein 3 and desmoglein 1. The presence of antibodies to desmoglein 3 is correlated with oral involvement, and the presence of antibodies to desmoglein 1 is correlated with skin involvement.
• The disease activity of pemphigus vulgaris correlates with antibody titers.
96
Q
A
Porokeratosis (Disseminated Superficial Actinic Type)
- The key histopathologic feature is a cornoid lamella, which is a column of parakeratotic cells beneath which there is absence or diminution of the granular layer as well as dyskeratotic or vacuolated keratinocytes.
- The linear type of porokeratosis has the greatest risk of malignant transformation to squamous cell carcinoma.
- genetic condition with many clinical forms
- solitary or multiple
- Porokeratosis of Mibelli is characterized by one or more round plaques with an atrophic center and a thin, elevated, keratotic border.
- Disseminated superficial actinic porokeratosis manifests as multiple, annular lesions with a hyperkeratotic, threadlike border on sun-exposed areas.
- Other variants include linear porokeratosis and punctate porokeratosis.
- The cornoid lamella corresponds clinically to the raised, keratotic or threadlike rim that is seen in lesions of porokeratosis.
- • Two cornoid lamellae may be present, often in disseminated superficial actinic porokeratosis type, and the intervening epidermis is often atrophic and hyperkeratotic. The dermis may demonstrate a bandlike, lichenoid inflammatory infiltrate, mimicking a lichenoid keratosis. Solar elastosis may be present.
- Multiple cornoid lamellae may be present in the linear and reticulated forms as well as in porokeratosis ptychotropica. Porokeratosis ptychotropica is a rare variant that manifests as verrucous papules in the perianal area.
97
Q
Dx criteria?
A
Mastocytosis
A diagnosis of systemic mastocytosis requires the major criterion:
- presence of multifocal compact mast cell clusters that exceed 15 cells in either bone marrow or any extracutaneous organs
4 minor criteria of which 3 must be fulfilled for a diagnosis of systemic mastocytosis.
- Spindled morphology in 25% or more of mast cells
- Aberrant CD2 and/or CD25 expression in mast cells
- A persistently elevated serum tryptase level of 20ng/mL or higher
- The presence of a KIT mutation involving codon 816.
99
Q
A
Reactive Perforating Collagenosis
- Reactive perforating collagenosis is a rare perforating disorder characterized by transepidermal elimination of altered collagen.
- Classic reactive perforating collagenosis is a genodermatosis inherited in an autosomal dominant or recessive manner, in which lesions are precipitated by trauma. The adult-onset, acquired type of reactive perforating collagenosis is associated with diabetes mellitus and chronic renal failure, especially in patients on dialysis, and is considered a type of acquired perforating dermatosis.
- Reactive perforating collagenosis is clinically characterized by papulonodules that have a central keratotic dell and resemble lesions of molluscum contagiosum or prurigo nodularis. The histologic combination of a saucer-shaped invagination containing neutrophilic debris and vertically oriented strands of collagen that have perforated through the epidermis is characteristic.
- Masson trichrome stain can be performed to confirm that the perforating fibers represent collagen. The collagen stains blue-green.
- Other forms of perforating disorders in the differential diagnosis of reactive perforating collagenosis include Kyrle disease, perforating folliculitis, and elastosis perforans serpiginosa. Kyrle diseases results in a cornified plug within an invaginated epidermis without follicular involvement. Perforating folliculitis shows a hyperkeratotic plug with basophilic debris associated with a follicular unit. Elastosis perforans serpiginosa demonstrates perforation of van Gieson-positive elastic fibers through the epidermis.
113
Q
GORLIN SYNDROME - NEVOID BCC SYNDROME
A
GORLIN SYNDROME - NEVOID BCC SYNDROME
- Genetics
- Autosomal dominant
- PTCH gene on chromsome 9q22.3 (regulateds Hedgehog pathway signaling)
- “2 hit” hypothesis
- Skin:
- multiple BCC before age 20
- palmar and plantar pits
- Nervous system:
- medulloblastoma
- Others:
- odontogenic keratocysts
- ovarian fibroma
- skeletal abnormalities
115
Q
A
BCC sclerosing/morpheaform
116
Q
A
Micronodular BCC
117
Q
A
Infiltrative BCC
118
Q
A
Fibroepithelioma of Pinkus
- long, thin, branching and anastomosing strands of basal cell carcinoma
- loose fibrovascular stroma
- many strands show a connection with the epidermis
- basaloid strands show 2 distinct-appearing cells
- lighter staining cell comprises the bulk of the strand
- scattered, small groups of darker cells are seen tapering off the main trunk in a palisading arrangement like buds on a branch
119
Q
A
Actinic Keratosis
- Scaly, “gritty,” erythematous thin non-indurated papule on sun damaged skin
- Atypia of the lower levels of the epidermis
- Atypia spares the follicles
- Alternating ortho and parakeratosis
- Solar Elastosis
120
Q
A
SCC IN SITU (BOWEN’S DISEASE)
- bulbous rete ridges, full thickness atypia, basal layer sparing (“eyeliner sign”)
- may show skip areas but involves follicles (in contrast to AKs)
121
Q
Age?
Gender?
Cause?
Genetics?
Prognosis?
A
Squamous Cell Carcinoma
- 2nd most common skin tumor
- Sun-exposed sites, older individuals, males > females
- Causes
- UV light exposure is most common
- Genetics
- TP53 mutations most common and are seen often at pyrimidine dimers
- Activating mutations in HRAS
- Loss of function mutations in Notch receptors
- Xeroderma pigmentosum
- Immunosuppression, HPV 5 and 8
- Other: industrial, chronic wounds, burn scars, arsenic, ionizing radiation
- Less than 5% metastasize
122
Q
A
KERATOACANTHOMA (KA) (PUTATIVE SCC)
- Low-grade tumor, rapid growth and spontaneous regression in most cases
- Histology:
- cup-shaped, symmetric keratin-filled lesion
- enlarged, glassy-appearing keratinocytes with squamous whorls
- acute inflammation
- infiltrative borders
- Controversial whether truly SCC or not, but may be aggressive in immunosuppressed pts.
123
Q
A
SEBORRHEIC KERATOSIS (SK)
- acanthosis with pseudohorn cysts
- papillations, +/- verrucoid
- clonal
- +/- irritated/inverted (inverted follicular keratosis) or pigmented
124
Q
A
EPIDERMAL NEVUS
- Clinical: usually children, head and neck, upper extremities
- Histology: variable, usually hyperkeratosis, acanthosis, papillomatosis
- may resemble SK or acanthosis nigricans
125
Q
A
CLEAR CELL ACANTHOMA
- acanthosis
- psoriasiform hyperplasia
- pale-staining keratinocytes (glycogen → PAS+/D-)
- mild spongiosis and neutrophils
126
Q
A
PILAR CYST (A.K.A., ISTHMUS-CATAGEN, TRICHOLEMMAL CYST)
- Clinical: usually scalp
- Histo: compact eosinophilic cyst contents w/trichilemmal (abrupt) keratinization, minimal/absent granular layer, calcification
127
Q
A
STEATOCYSTOMA MULTIPLEX
- undulating squamoid epithelium with corrugated eosinophilic lining
- lacks keratin debris
- often a/w sebaceous glands or follicular structures
128
Q
A
HIDROCYSTOMA
- Head and neck, solitary lesions, most are apocrine (few “eccrine”)
- Flattened to columnar 1-2 cell lining, often with snouting and decapitation secretion
130
Q
A
SYRINGOMA
- Clinical: multiple small flesh-colored papules on the face of a woman, Asians
- Histo: bland ductal structures with occasional cords and tadpole-shapes in a fibrotic stroma
- DDx: desmoplastic trichoepithelioma (follicular diff, calcs), MAC (follicular cysts, deep and perineural invasion)
131
Q
A
POROMA
- anastomosing strands of bland adnexal keratinocytes
- originates from epidermis, extends into dermis
- focal duct formation (closely related to hidradenoma and dermal duct tumor)
132
Q
A
HIDRADENOMA
- dermal nodule
- well-circumscribed
- eosinophilic or clear-staining cells, with apocrine & variable ductal differentiation
133
Q
A
SPIRADENOMA (“ECCRINE SPIRADENOMA”)
- Lobules and nests of adnexal cells
- 2 epithelial cell types
- smaller outer dark cells
- larger inner pale cells
- Often eosinophilic hyaline droplets, or cylindar formation, cystic spaces, prominent vessels, hemorrhage
- Likely apocrine
134
Q
A
CYLINDROMA
- “Jigsaw puzzle” pattern of irregularly-shaped, well-circumscribed nests separated by thickened basement membrane
- Occasional ducts (much less than spiradenoma), may also see hyaline droplets
- likely apocrine
135
Q
A
HIDRADENOMA PAPILLIFERUM
- Clinical: perineal region of women
- Histo: dermal-based nodule of tubular and cystic structures with apocrine differentiation
136
Q
A
MICROCYSTIC ADNEXAL CARCINOMA (MAC)
- Clin: depressed plaque on face, esp. lip, young adults
- Histo:
- Superficial bland follicular cysts
- deeply infiltrative epithelial strands with follicular and sweat duct formation
- often perineural invasion
DDx:
- Sclerosing BCC: lacks superficial follicular cysts and ductal diff’nt, rare perineural invas, hi Ki-67
- Desmoplastic trichoepithelioma: lacks deep invasion or perineural invasion, has calcifications, follicular but no ductal diff’nt; neg CK7, EMA
137
Q
A
EXTRAMAMMARY PAGET’S DISEASE
- Clinical: eroded plaque, usually genital or perineal area, but also axilla and eyelid
- Histo: pagetoid intraepidermal spread of large, cytologically atypical, pale to foamy-appearing cells, occasional signet ring or gland formation
- mucin and PASD+
- IHC: CEA+, GCDFP+, CAM5.2+, EMA+, CK7+; CK20-, S100-
138
Q
A
SEBACEOUS ADENOMA
- Papule/nodule on face/scalp
- +/- Muir Torre syndrome
- especially if multiple or cystic lesions
- HNPCC
- MLH1, MSH2, MSH6
- Histo:
- well-circumscribed growth
- > 50% well-differentiated sebocytes
- no atypia
139
Q
A
Sebaceous hyperplasia
- most common sebaceous gland lesion
- elderly, umbilicated yellowish papules on nose or cheeks
- Histology:
- expansion of normal lobular sebaceous gland architecture
- no thickening of peripheral germinative layer of seboblasts
140
Q
A
SEBACEOMA (“SEBACEOUS EPITHELIOMA”)
- +/- Muir Torre syndrome
- especially if multiple or cystic lesions
- HNPCC
- MLH1, MSH2, MSH6
- Histo:
- circumscribed growth
- < 50% well-differentiated sebocytes
- > 50% basaloid cells
141
Q
A
SEBACEOUS CARCINOMA
- Clinical:
- eyelids > head and neck
- aggressive tumor
- Histology:
- infiltrative growth pattern, +/- pagetoid spread
- should find vacuolated cells
- marked atypia, +/- squamous or basaloid differentiation
- IHC: Adipophilin+, CK7+, CAM5.2+, Androgen R+, EMA± (lost in poorly diff’nt); GCDFGP-, CEA-
- high p53 & Ki-67 (low in adenoma/sebaceoma)
142
Q
A
FOLLICULAR NEOPLASMS: TRICHOEPITHELIOMA/TRICHOBLASTOMA
- Familial cases
- 9q21, mutation in tumor suppressor gene
- PTCH, 9q22.3 (BCC) also involved
- CYLD (cylindromatosis oncogene), 16q12-q13
- Brooke-Spiegler syndrome
- familial cylindromatosis
- multiple familial trichoepithelioma
- Clinical:
- head and neck, young to aging adults
- hereditary form may be younger
- Histology:
- basaloid nodules with palisading
- keratinous microcysts (often calcified)
- papillary mesenchymal bodies (hair papillae-like structures)
- fibrotic stroma, lacks mucin
- Desmoplastic TE shows more infiltrative features
- DDx: BCC (mucin, clefting, increased mitoses and apoptoses), MAC (deeper, perineural invasion)
143
Q
A
FOLLICULAR NEOPLASMS: PILOMATRIXOMA
- Clinical:
- slowly growing, solid nodule on head and neck
- children/young adults
- Histology:
- biphasic population of dark basaloid cells merging with palely eosinophil “ghost cells”
- calcifications common, even bone formation
144
Q
A
SPITZ NEVUS
- Symmetric, well-circum, usually compound proliferation w/ epidermal hyperplasia
- Spindled and epithelioid cells, vertically oriented junctional nests w/streaming (“raining down” appearance)
- Clefting and Kamino bodies (eosin globules)
145
Q
A
REED’S/PIGMENTED SPINDLE CELL NEVUS
146
Q
A
PALISADED ENCAPSULATED NEUROMA (PEN)
- Clinical: small papule on the face
- Histo: upper dermis, circumscribed proliferation of fascicles; stroma less myxoid than neurofibroma; no Verocay bodies
