Dermatopathology Flashcards
1
Q
Skin
Functions
A
- Protective barrier against mechanical, thermal and physical injury as well as noxious agents
- Prevents loss of moisture
- Reduces harmful effects of UV radiation
- Acts as a sensory organ
- Helps regulate temperature control
- Plays a role in immunological surveillance
- Synthesizes vitamin D3 (cholecalciferol)
- Has cosmetic, social, and sexual associations
2
Q
Skin
Layers
A
-
Epidermis
- External layer
- Mainly composed of layers of keratinocytes
- Also containing melanocytes, Langerhans cells and Merkel cells
- Basement membrane
- Multilayered structure forming dermal-epidermal junction
-
Dermis
- Area of supportive connective tissue between epidermis and underlying subcutis
- Contains sweat glands, hair roots, nervous cells and fibers, blood and lymph vessels
-
Subcutis
- Layer of loose connective tissue and fat beneath dermis
3
Q
Epidermal
Layers
A
4
Q
Acantholysis
A
Loss of intercellular cohesion between keratinocytes
Loss of cell-cell adhesion
Ex. Pemphigus
5
Q
Regular
Acanthosis
A
↑ in thickness of epidermis
Regular ⇒ all rete pegs descend to same level
Ex. Psoriasis
6
Q
Irregular
Acanthosis
A
↑ in thickness of epidermis
Irregular ⇒ rete pegs descend to different levels in papillary dermis
Ex. Lichen Simplex Chronicus
7
Q
Civatte/Colloid Bodies
A
Pink, globular remnants of keratinocytes
Ex. Lichen Planus
8
Q
Epidermal Atrophy
A
↓ thickness of epidermis
Ex. Actinic Keratosis
9
Q
Dyskeratosis
A
- Abnormal, premature keratinization w/in cells below stratum granulosum
- Corps rond ⇒ rounded nucleus w/ halo of pale to pink dyskeratotic cytoplasm
- Grain ⇒ dark blue flattened nucleus surrounded by minimal dyskeratotic cytoplasm
- Ex. Darier’s Disease
10
Q
Erosion
A
Loss of epidermis
11
Q
Exocytosis
A
- Lymphocytes in epidermis w/ associated spongiosis
- Term usually used when discussing spongiotic dermatitis
12
Q
Hydropic Swelling
(Ballooning)
A
- Intracellular edema of keratinocytes
- Often seen in viral infections
- Ex. Herpes Simplex
13
Q
Hyper-/Hypogranulosis
A
↑/↓ granular layer
14
Q
Hyperkeratosis
A
Thickening of stratum corneum
15
Q
Lentiginous Melanocytic
Growth Pattern
A
Linear pattern of melanocyte proliferation w/in epidermal basal cell layer
16
Q
Papillomatosis
A
- Surface elevation caused by hyperplasia and enlargement of contiguous dermal papillae
- Finger-like projections
17
Q
Parakeratosis
A
- Keratinization w/ retained nuclei in stratum corneum
- On mucous membranes, parakeratosis is normal
18
Q
Spongiosis
A
Intercellular edema in epidermis w/ stretching of cell-cell junctions
19
Q
Freckle (Ephelis)
Overview
A
- Small, well-defined, pigmented macules
- 1–2 mm in diameter
- Predilection for face, arms, and shoulder regions of fair-skinned individuals
- Appear at an early age and may follow an episode of severe sunburn
20
Q
Freckle (Ephelis)
Histopathology
A
↑ melanin pigment w/in basal keratinocytes ⇒ Hyperpigmentation of freckles
Melanocytes are normal in number and morphology
21
Q
Lentigo Simplex
A
- Brown macule w/ an early age of onset
- Little or no relationship to sun exposure
- Hyperpigmented
- Often elongated rete ridges
- Usually w/ ↑ melanocytes
- No nests of melanocytes
22
Q
Benign Melanocytic Nevi
Overview
A
Junctional, Compound, or Intradermal nevus:
-
Junctional Nevus
- Brown to black macule w/ melanocytic nests at junction of epidermis and dermis
-
Compound Nevus
- Brown papule w/ combined histologic features of junctional and intradermal nevi
-
Intradermal Nevus
- Skin-colored or light brown papule w/ nests of melanocytes in dermis
23
Q
Benign Melanocytic Nevi
Histopathology
A
- Epidermal changes vary greatly
- Atrophy, hyperplasia, papillomatosis or horn cysts may be present
- Nests at dermal-epidermal junction and/or in dermis
- Bilaterally symmetrical & sharply defined
-
Individual cells mature
- Important in distinguishing some benign nevi from melanomas (usually show little or no maturation)
-
Superficial nevus cells are larger
- Tend to produce melanin
- Grow in nests
-
Deeper nevus cells are smaller
- Produce little or no pigment
- Appear as cords and single cells
24
Q
Seborrheic Keratoses
Overview
A
- Common benign lesions
- Typically begin to appear during 4th decade of life
-
Tan to black macular, papular or verrucous lesions
- Solitary or multiple
- Often have a waxy, velvety or verrucous, ‘stuck-on’ appearance
- Large variation in clinical appearance
- May simulate melanocytic neoplasms
25
Q
Leser–Trélat
Sign
A
- Abrupt ↑ in size or number of seborrheic keratoses
- Paraneoplastic cutaneous marker associated w/ an internal malignancy
26
Q
Seborrheic Keratoses
Histopathology
A
- Epidermal proliferation
- Variable combinations of hyperkeratosis, papillomatosis, acanthosis
- Keratinocytes often appear basaloid
- Often have pseudo-horncysts
- “Pseudo” b/c they connect to surface and represent papillomatosis
- Often abundant melanin in basal layer or throughout epidermis
27
Q
Skin Tag / Acrochordon / Fibroepithelial Polyp
A
- Skin-colored to brown papules of eyelids, neck, axilla or groin
- Often pedunculated
- Very common
- ↑ incidence w/ aging and obesity
28
Q
Skin Tag
Histopathology
A
- Pedunculated papule
- Epidermis often extends almost completely around specimen when sectioned
- Papillomatosis and acanthosis common
- ± Epidermal atrophy
- Dermis consists of loose CT that is often pale
- Dilated blood vessels common
29
Q
Cysts
Overview
A
- Walled-off cavity filled w/ keratin, mucin or fluid
- Classified based on location, contents, type of epithelial lining, and adnexa presence
- Clinical manifestation:
- Firm, well-circumscribed, dermal or subcutaneous nodules
- Often moveable
30
Q
Epidermal Inclusion
Cyst
A
- Contains lamellated keratin
- Lined by squamous epithelium
- Sometimes flattened w/ a granular layer
31
Q
Pilar or Trichilemmal
Cyst
A
- Contains amorphous, dense and compact, homogenized keratin
- Lined by squamous epithelium
- Keratinocytes are often pale
- There is no granular layer
- Calcification common w/in cyst
32
Q
Dermoid
Cyst
A
- Wall commonly resembles epidermoid cyst
- Lined by squamous epithelium
- Contains multiple appendages budding outward from its wall
- Small hair follicles
- Sebaceous glands
- Eccrine glands
- Apocrine glands
33
Q
Steatocystoma
A
- Cyst wall consists of rugated squamous epithelium
- Wrinkled eosinophilic refractile cuticle of keratin instead of a granular layer
- Sebaceous glands w/in or adjacent to cyst wall, opening into cyst
- Only “true” sebaceous cyst
34
Q
Actinic Keratosis
Overview
A
- Common, precancerous ill-defined white-red papule
- Found in sun-damaged areas
- low-grade atypia of epithelium vs precursor lesion to early low-grade carcinoma in situ
- analogous lower grade lesion of intraepithelial neoplasia seen in cervix or vulva
35
Q
Actinic Keratosis
Histopathology
A
- Often hyperkeratosis
- Sometimes ulceration
- Parakeratosis especially overlying atypical keratinocytes
- Partial-thickness atypical keratinocytes
- Nuclear pleomorphism
- Atypical mitosis
- Disordered maturation
- Often spares epidermis above adnexa
- Solar elastosis in dermis
36
Q
Squamous Cell Carcinoma In Situ
Overview
A
“Bowen’s disease”
- Common hyperkeratotic erythematous plaque
- Often crusted on sun-exposed or covered skin
- Full-thickness atypia of epidermal keratinocytes over a broad zone
37
Q
Squamous Cell Carcinoma In Situ
Histopathology
A
- Parakeratosis, hyperkeratosis, acanthosis
- Atypical keratinocytes with
- Nuclear pleomorphism
- Atypical mitosis
- Disordered maturation throughout epidermis (all layers)
- Atypical keratinocytes have not invaded through BM of dermal-epidermal junction
38
Q
Squamous Cell Carcinoma
Overview
A
- Second most common type of skin cancer
- Red papule, nodule or plaque
- Often hyperkeratotic or ulcerated
39
Q
Squamous Cell Carcinoma
Histopathology
A
- Invasion of dermis by atypical keratinocytes
- Cells w/ nuclear pleomorphism, atypical mitosis and disordered maturation
- Keratinocytes enlarged w/ abundant ground-glass eosinophilic cytoplasm
- ± Polymorphous inflammatory infiltrate
40
Q
Basal Cell Carcinoma
Overview
A
- Most common type of skin cancer
- Pearly erythematous papule w/ rolled border
- Usu. on head and neck region
- Long-standing lesions often large, locally destructive, and ulcerated ⇒ “rodent ulcer”
41
Q
Melanoma
Overview
A
- Malignant tumor arising from melanocytes
- Usually presents as:
- Enlarging, irregularly pigmented macule, papule, or plaque
- Asymmetric w/ irregular borders
- ↑ Incidence and mortality rates of melanoma in recent decades
- Early detection important in melanoma management
42
Q
Melanoma
Histopathology
A
- Epidermis normal, atrophic or hyperplastic
- Ulceration means worse prognosis
- Asymmetrical proliferation of melanocytes
- Often w/ poorly demarcated border
- Atypical melanocytes
- Small, spindled or epitheloid
- Often finely dusted w/ melanin
- Arise at dermal-epidermal junction
- Invade the dermis
- Pleomorphism, hyperchromatism, ↑ mitoses and ± prominent nuclei
- Poor maturation of melanocytes
- Deeper cells are just as large and atypical as superficial one
- Pagetoid spread (or buckshot scatter) of melanocytes w/in epidermis
- Lymphocytic infiltrate at base common
- Depth of invasion into dermis ⇒ Breslow’s thickness
- Most important prognostic factor
43
Q
Basal Cell Carcinoma
Histopathology
A
- ± Ulceration of epidermis
- Basaloid tumor cells
- Buds from epidermis or follicles or found w/in dermis
- Variable atypia
- Stroma often separates from tumor ⇒ Retraction artifact
- Peripheral palisading of nuclei
- Mucin in stroma or w/in basaloid aggregates
44
Q
Tumors of the Dermis
A
45
Q
Dermatofibroma
Overview
A
- Common benign fibrohistiocytic tumors of the skin
- Firm dermal papules that “dimple” when the adjacent skin is compressed
46
Q
Dermatofibroma
Histopathology
A
- Epidermal hyperplasia
- Flattened “tabled” rete ridges or basaloid proliferation
- Hyperpigmented basal layer
- Poorly circumscribed proliferation of boomerang-shaped spindled fibroblasts or histiocytes in the dermis
- Often w/ whorled appearance
- Large bundles of collagen (“keloidal collagen”) often present at periphery of lesion
- Fibroblast around the bundles ⇒ “collagen trapping”
47
Q
Cellular Migrant
Skin Tumors
A
- Proliferative disorders of the skin involving cells whose progenitors arise elsewhere
- Hone in to the cutaneous microenvironment
48
Q
Cutaneous T-Cell Lymphomas (CTCL)
Overview
A
- Primary cutaneous disorders that arises from lymphocytes
-
Mycosis fungoides (MF) ⇒ most common type of CTCL
- Accounts for ~ 50% of all primary cutaneous lymphomas
- Classical MF ⇒ progress from patch stage → plaque stage → tumor stage
- Long clinical course over years or even decades
49
Q
CTCL
Histopathology
A
-
Early lesions ⇒ band-like infiltrate of slightly atypical lymphocytes
- Line up along the dermal–epidermal junction
-
As lesions progress ⇒ progressive epidermotropism of atypical lymphocytes
- Epidermotropism = lymphocytes residing in the epidermis
- Often exhibits a peripheral halo
- Numerous lymphocytes w/in the epidermis w/ minimal spongiosis
- Focal collections of intraepidermal atypical lymphocytes ⇒ Pautrier microabscesses
- Most specific finding
- Only in 10% of lesions
- Atypical lymphocytes sometimes have cerebriform nucei
- Tumor stage ⇒ less epidermotropism and atypical lymphocytes diffusely fill the dermis
50
Q
Urticaria
Overview
A
- Transient skin or mucosal swellings due to plasma leakage
- Wheals are characteristically pruritic and pink or pale in the center
51
Q
Urticaria
Histopathology
A
- Epidermis normal
- Dermal edema
- Sparse perivascular and interstitial eosinophils, lymphocytes, PMNs and/or mast cells
52
Q
Eczematous Dermatitis
Overview
A
- Diseases under umbrella category of “eczematous dermatoses”
- Similar clinical and histological presentations
- Eczema means to “boil over” and is synonymous w/ dermatitis
- Spongiotic inflammation of the epidermis ⇒ common unifying characteristic
53
Q
Eczematous Dermatitis
Diseases
A
- Allergic contact dermatitis
- Asteatotic dermatitis
- Atopic dermatitis
- Autosensitization (ID) reaction
- Dyshidrotic eczema
- Irritant contact dermatitis
- Nummular dermatitis
- Seborrheic dermatitis
- Venous stasis dermatitis
54
Q
Eczematous Dermatitis
Histopathology
A
- Hallmark is spongiosis ⇒ exocytosis of lymphocytes and intercellular edema
- ± Spongiotic vesicle (more likely if clinically acute)
- Focal parakeratosis w/ ± crusting
- PMNs in stratum corneum if secondarily impetiginized
- Acanthosis or hyperkeratosis (more if clinically chronic)
- Superficial perivascular lymphocytes, occasional eosinophils
55
Q
Erythema Multiforme
Overview
A
- Most commonly associated w/ herpes simplex virus (HSV) infection
- Typical clinical presentation includes “target” lesions
- Oral mucosa, dorsal hands, or palms frequently involved
- Episodes are recurrent and self-limited
56
Q
Erythema Multiforme
Histopathology
A
- Necrotic keratinocytes
- ± Spongiosis
- Rarely intraepidermal vesicles
- Basal layer liquefaction w/ ± subepidermal blister
- Edema of the papillary dermis
- Perivascular or interface lymphocytes, rarely w/ eosinophils
57
Q
Chronic Inflammatory Dermatoses
A
Inflammatory skin disorders that persist for many months to years
58
Q
Psoriasis
Overview
A
- Chronic disorder
- Results from a polygenic predisposition combined w/ triggering factor
- E.g. Trauma, infections or medications
- Sharply demarcated, scaly, erythematous plaques
- ± Sterile pustules
- Most common sites:
- Scalp, elbows and knees
- Nails, hands, feet and trunk (including intergluteal fold)
59
Q
Psoriasis
Histopathology
A
- Confluent parakeratosis
-
PMNs in:
- Stratum corneum ⇒ Munro microabscesses
- Spinous layer ⇒ spongiform pustules of Kogoj
- Hypogranulosis
- Suprapapillary thinning of epidermis
- Regular acanthosis, often w/ clubbed rete ridges
- Dilated capillaries in dermal papillae
- Auspitz sign ⇒ pinpoint bleeding if scale picked off
- Perivascular lymphocytes
60
Q
Lichen Planus
Overview
A
- “Pruritic, purple, polygonal, planar papules and plaques” of skin and mucosa
- Fine reticulated scale over surface ⇒ Wickham’s striae
- Hep C is more prevalent in pts w/ lichen planus vs controls
61
Q
Lichen Planus
Histopathology
A
- Compact hyperkeratosis
- No parakeratosis
- Hypergranulosis, often wedge shaped
- Irregular acanthosis w/ “saw-toothed” rete ridges
- Colloid/civatte bodies
- Dense, continuous infiltrate of lymphocytes along D-E junction
- Liquefaction degeneration of the basal layer ⇒ ex. Of interface dermatitis
- Melanin incontinence common
62
Q
Blistering (Bullous) Diseases
A
Classified by:
- Level of the blister
- Subcorneal, intraepidermal, subepidermal
- Type of inflammatory cells involved
- PMNs, lymphocytes, eosinophils
- Mechanism of blister formation
- Spongiosis, acantholysis, balloon degeneration or epidermolysis
63
Q
Pemphigus Vulgaris
Overview
A
- Intraepidermal vesiculobullous disorder
- Caused by auto-Ab directed at an intercellular keratinocyte adhesion protein ⇒ Desmoglein 3
- Presents w/ flaccid bullae that break to form painful erosions
64
Q
Pemphigus Vulgaris
Histopathology
A
- Split immediately above basal layer
- Leaves a “tombstone row” of basal keratinocytes
- Tracking of separation down hair follicles ⇒ “follicular extension”
- ± Eosinophils in spongiotic foci or blister cavity
- Superficial lymphocytic inflammatory infiltrate in dermis
- ± Eosinophils in dermal infiltrate
- Direct IF (DIF) shows “net-like” deposition of IgG and C3 between keratinocytes in lower epidermis
65
Q
Bullous Pemphigoid
Overview
A
- Subepidermal vesiculobullous disorder
- Caused by auto-Ab to bullous pemphigoid antigen I and/or bullous pemphigoid antigen II
- Presents with:
- Tense bullae on normal or erythematous skin
- Urticarial/eczematous lesions
66
Q
Bullous Pemphigoid
Histopathology
A
- Subepidermal bulla
- Eosinophils typically present w/in blister cavity
- Early lesions ⇒ ± eosinophilic spongiosis
- Exocytosis of eosinophils w/in a mildly spongiotic epidermis
- Direct IF of adjacent skin shows linear deposition of IgG and C3 along D-E junction
67
Q
Dermatitis Herpetiformis
Overview
A
- Intensely pruritic vesiculobullous disorder
- Lesions common on elbows, knees, buttocks, and scalp
- Caused by auto-Ab vs epidermal transglutaminase-3
- Disease is highly correlated w/ celiac sprue
68
Q
Dermatitis Herpetiformis
Histopathology
A
- Subepidermal vesiculation
- Neutrophilic abscesses in tips of dermal papillae
- Slight fibrin deposition in tips of dermal papillae @ points of vesiculation
- Direct IF shows granular deposition of IgA w/in dermal papillae
69
Q
Acne Vulgaris
Overview
A
- Multifactorial disorder of the pilosebaceous unit
- Significant psychologic and economic impact
- Clinical manifestations include comedones, papules, pustules, cysts and scarring
- Characterized by:
- ↑ Sebum production
- Follicular hyperkeratinization
- Propionibacterium acnes
- Inflammation
70
Q
Acne Vulgaris
Histopathology
A
- Follicular plugging
- Frequently ruptured pilosebaceous apparatus w/ suppurative inflammation
- Sometimes abscesses, sinus tracts and fibrosis
71
Q
Panniculitis
A
- Inflammation of the subcutaneous fat
- Categorized into 2 groups:
- “Septal” ⇒ primarily involves the septa separating lobules of fat
- “Lobular” ⇒ primarily involves the lobules of fat themselves
72
Q
Erythema Nodosum
Overview
A
- Painful, erythematous subcutaneous nodules
- Usually distributed symmetrically over pretibial areas; occasionally elsewhere
- Later stages ⇒ lesions acquire a bruise-like appearance
- ± Fever, arthralgias and malaise
- Associated w/ a wide variety of systemic disorders
73
Q
Erythema Nodosum
Histopathology
A
- Septal panniculitis of lymphocytes, histiocytes, PMNs and/or eosinophils
- Older lesions:
- Multinucleated giant cells
- Septal fibrosis
74
Q
Verrucae
Overview
A
“Warts”
-
Caused by human papillomavirus (HPV)
- Ubiquitous DNA virus
- Over 100 HPV subtypes
- Different subtypes tend to produce different clinical lesions
- Immunocompromised patients may have larger or more intractable warts
75
Q
Verrucae (Warts)
Histopathology
A
- Hyperkeratosis, papillomatosis, hypergranulosis
- Columns of parakeratosis
- Especially over projecting dermal papillae
- Vacuolated superficial keratinocytes w/ pyknotic raisin-like nuclei ⇒ koilocytes
- Rete ridges shaped inward @ borders of lesion
- Dilated capillaries in dermal papillae
- Perivascular lymphocytes
76
Q
Molluscum Contagiosum
A
- Caused by a DNA poxvirus of the Molluscipox genus
- Mainly a disease of children
- Can affect immunocompromised adults
- Produces smooth, dome-shaped, umbilicated papules
77
Q
Impetigo Contagiosa
Overview
A
- Common superficial infection w/ Staph aureus and/or Strep pyogenes
- Most common in children
- Plaques of honey-colored crust
78
Q
Impetigo Contagiosa
Histopathology
A
- Early lesions ⇒ subcorneal pustule filled w/ PMNs ± acantholytic cells
- Spongiosis common
- Established lesions ⇒ crust composed of serum, PMNs and parakeratotic material
- Gram-⊕ cocci usually found in crust
- Gram stain and culture may be required
79
Q
Dermatophytosis (Tinea)
Overview
A
- Caused by superficial fungi
- Further subclassified based on area of the body affected
- Most tinea infections are characterized by:
- Intensely pruritic, annular lesions
- Peripheral scale
- Central clearing
- Variable inflammation
80
Q
Dermatophytosis (Tinea)
Histopathology
A
- ± PMNs in the stratum corneum
- Parakeratosis common
- Fungal hyphae in stratum corneum or follicles
- Sometimes visible w/ H&E
- Best seen w/ Periodic Acid–Schiff (PAS) stain
- Rich in mucopolysaccharides ⇒ stain bright pink to red
- Variable inflammatory response
- Skin may appear “normal”
- Culture of material scraped from these areas will usu. allow ID of offending species
81
Q
Pityriasis Versicolor
Overview
A
- Superficial infection of the epidermis caused by commensal yeast of genus Pityrosporum
- Some use the genus Malassezia to refer to the pathogenic hyphal phase of this normal skin commensal
- Particularly common in young adults living in warm and humid climates
- Hypopigmented or brownish-red, slightly scaly patches
- Most common on the trunk
