Dermatopathology
1. Premalignant & Malignant Epithelial Tumors
Actinic Keratosis: epith. dysplasia introduced by UVR; more common in fair skinned people; UVR damages keratinocyte DNA
(poss. Langerhans’s cells)
Gross: rough, red w/ indistinct borders
Micro: epith. dyplasia in lower1/3 of epidermis; solar elastosis in dermis
Comment: can become SCC; may regress; treat early b/c of unknown progression
Squamous Cell Carcinoma (SCC): most arise from AK’s; carcinogens, chronic ulcers; scars, arsenic, HPV, and radiation can also
be factors; individuals w/ DNA repair defects and/or imm.supp. (i.e. transplant) are at greater risk
G: flesh colored to red; often scaly; CIS (Bowen’s) often presents as scaly erythematous plaque resembling psoriasis
M: Nodular proliferation of dysplastic keratinocytes; “fingers” of tumor may infiltrate derm.; CIS replaces epid. w/ atyp. keratinocyte
C: UV induced SCC of skin rarely (5%) metastasizes to regional nodes; other precursors (i.e.scars) = more aggressive; actinic SCC of
mucous membrane = more likely to metastasize
Basal Cell Carcinoma (BCC): most common cancer; rarely metastasizes but is hematogenous; occurs on sun exposed areas but is
not as directly related as SCC
G&M: Three presentations: 1. Noduloulcerative: translucent telangiectatic papule +/- ulcer; nodular prolif. of basaloid cells in a
fibromucinous stroma, may have infiltrating tumor at the deep aspects of the tumor
2. Superficial: scaley red patch; mult. buds of basaloid tumor cells along derm/epiderm jxn
3. Sclerosing: scar-like plaque; infiltrating slender strands of basaloid tumor cells in fibrous stroma
-all tend to show peripheral nuclear palisading
C: Patients w/ basal cell nevus syndrome may have hundreds of tiny BCC’s; some lesions may become quite destructive if ignored;
other signs of this phenotype include frontal losing jaw, cysts, and bifid ribs; these pts. have PTC gene mutations.
Merkel Cell Carcinoma: rare cutaneous neuroendocrine CA that may be lethal or mistaken for BCC
Melanoma: may also occur on mucosal surfaces, leptomeninges, uveal tract of eye; sunlight is only 1 factor; genetics can play a role
(i.e. dysplastic nevus syndrome)
G: ABCD’s: Asymmetry, Border irregularity, Color heterogenieity, Diameter > 6mm
M: Growth phases: Radial (can’t metastasize) 1. Pagetoid – larger cells w/ buckshot scatter of atyp. cells at all levels of epid.
2. Lentiginous – cells singly & in nests along derm/epider jxn; extend into appendages
Vertical (tumorigenic-can metastasize) – nodule of atypical cells growing into dermis
C: 4 classic types: Superficial spreading (Pagetoid)
Lentigo maligna
Acral Lentiginous
Nodular – differs from other 3 b/c it has no radial phase; other have radial to vertical progression
2. Malignant Dermal Tumors
Dermatofibrosarcoma Protuberans (DFSP): one of many dermal and subcuticular sarcomas
G: nodule or plaque (may be several cm’s) w/ nodules in it
M: “Storiform” pattern; often infiltrates fat; clear surgical margins difficult, CD34 +
C: rarely metastasize but are destructive (even larger than BCC)
3. Malignant Tumors of Cellular Immigrants to the Skin
Histiocytosis X (Langerhans cells histiocytosis): several variants; book refers to Letterer-Siwe variant
G: Letterer-Siwe disease often looks like seborrheic dermatitis with tiny hemangiomas
M: Several patterns exist but at least some histiocytes are present (w/ foam cytoplasm); eosinos & Lycs are also present; the
characteristic cell contains organelles called “Birbeck Granules” and marks w/ S-100 protein and CD1a
Cutaneous T-Cell Lymphoma (CTCL): skin involvement w/ poss. leukemia
G: several presentations including: red scaly patches; plaques and nodules; diffuse itchy red scaly skin
M: due to clonal prolif. of malignant CD4 positive Lycs (Sezary-Lutzner cells – clusters of these cells = Pautrier micro-abscesses)
C: Mycosis fungiodes = CTCL w/ patches or plaques and or nodules(tumors)
Erythroderma + Leukemia = Sezary Syndrome
4. Disorders of Pigmentation and Melanocytes
Vitiligo: patchy hypo/depigmentation due to malanocyte damage/loss (unknown mech.); albinism = absence of tyrosinose
Freckle (ephilis): tan-brown macules on sun-exposed skin
M: hyperpigmentation of rete; NO proliferation of melanocytes (unknown mech.)
Melasma: patchy facial and neck hyperpigmentation (often mask-like)
M: Epidermal type has hyperpigmented basal layer of keratinocytes; Dermal type has incontinent melanin in papillary dermis
C: cause = Hm’s?; classically occurs w/ pregnancy (“Mask of Pregnancy”)
Lentigo = Melanocytic Nevi
5. Benign Epithelial Tumors
Seborrheic Keratosis (SK): benign keratinocyte prolif. in mid-older people
G: rough (warty); flesh colored to brown/black; on trunk; looks “Stuck on”
M: proliferation of basaloid keratinocytes, may be squamoid; cystic foci of lamellated keratin (horn pseudocyst)
C: tiny dark SK’s on face of darker skinned people are called “Dermatosis Papulosa Nigra”; rapid occurrence of large #’s of SK’s
may be assoc. w/ internal malignancy (Leser-Trelat sign)
Acanthosis Nigricans: common in obese young-mid aged people; may signify hyperinsulinemia (->Type II DM); may actually be
easier to see on extensor surfaces of joints, elbows, knees, toes, than on neck; skin is folded rather than thickened.
Fibroepithelial Polyps (aka skin tag, acrochondron, squamous papilloma): may be assoc. w/ acanthosis nigricans and DM; some
on the neck may have thick SK-like epith. while others may have a more fibrous core.
Epitheloid Cysts: 90% of all cutaneous cysts; most from follicular infundibulum; epidermal inclusion cysts due to injury do occur;
acne cysts are epidermoid cysts
G: dome shaped nodule w/ poral opening fixed to epidermis; may be multiple
M: wall and cyst keratin look like surface skin
Trichilemmal (Pilar) Cysts: about 10% of cysts; mainly on scalp; multiple ones inherited as AD trait (women)
G: dome shaped papule fixed to epidermis; NO pore; may be firmer
M: lining like middle part of hair follicle; pink homogenous keratin
Dermoid Cysts: rare but most common on face of infant; lined like epidermoid cyst but have tiny hair follicle elements (sebaceous)
Steatocystoma: single or multiple oily centered w/ sebaceous glands in wall; on trunks of teenagers and older people
Keratoancanthoma: “self healing squamous cell carcinoma”; classic type is a rapidly growing nodule w/ a keratin filled center
Appendage tumors: flesh colored papules and nodules: table 27-2, p.1183
Nevocellular Nevi: melanocytic “nevi” are benign tumors of melanocytes; may go thru many forms in life cycle; “Mole” is the
common term for “melanocytic nevus”; types of nevi have general areas of occurrence; most fair-skinned people get 40 or so moles in
a lifetime (few after age 40); UVR seems to play a role
G& M: Lentigo simplex = 1-2mm brown/black macule - hyperpig.,  #’s of melanocytes at tips of rete ridges
Junctional nevus = 2-3mm “ (distal extremities) – clusters of melanocytes and hyperpig. at tips of rete
Compound nevus = 3-5mm brown papule (trunk and prox. extremities) – clusters of same and nests/sheets/strands of nml
Intradermal nevus = 3-5mm flesh colored papule (face) – junctional component disappears leaving the dermal component;
older lesions may resemble neurofibromas or be fat infiltrated
-cytological atypia is absent
C: some variants on the theme of melanocytic nevus are on P. 1176
Dysplastic Nevi: poss. a percusor for melanoma esp. in patients w/ dysplastic nevus syndrome (rare AD trait in which people develop
large #’s of dysplastic nevi in late childhood); felt to be abbherant differentiation of common nevi; sporadic occurences mean nothing.
G: predominately on trunk and prox. extremities; larger than common nevi and have some border and color irregularities
M: may be junctinal or compound; lentiginous proliferation of melanocytes singly and in nests; lateral bridging of one rete to another;
concentric and lamellar dermal fibrosis; patchy lymphocytic infiltrate at base of melanocytic proliferation; +/- cellular atypia
6. Benign Dermal Neoplasms
Benign Fibrous Histiocytoma (Dermatofibroma, DF) – may not be a true neoplasm
G: Firm dermal papule that indents when pressed on sides (dimple sign); reddish tan to brown/black; most commonly occur on
women’s legs; may be mult.; assymp.
M: more or less circumscribed proliferation of spindled fibroblasts; may appear to trap normal collagen bundles; some foamy macros;
CD 34 neg.
Xanthomas: not neoplasms but collections of foamy macrophages often assoc. w/ hyperlipidemia; types include eruptive(fleshy),
tuberous and tendinous(yellow nodules), plane(streaks), xanthelasma (eyelids – may not be assoc. w/ hyperlipidemia)
Cherry Angiomas: common tiny capillary hemangiomas in adults; no indication of internal disease
Strawberry Hemangiomas: rapidly growing capillary hemangiomas in infants; may involute; particularily likely to have internal
organ involvement if mult. lesions aare present
Benign Tumor of Cellular Imigrants to the Skin
Mastocytosis: Variants: 1. Mastocytoma: one or a few lesions; localized dermal nodule of mast cell infiltration; urticate, blister if
rubbed (Darier sign); involutes eventually
2. Urticaria pigmentosa: lesions like mastocytomas but usually slightly smaller/more numerous;
tachycardia & diarrhea may occur to due release of hist. if rubbed vigorously
3. Diffuse intracutaneous mastocytosis: diffuse skin infiltration w/ mast cells; diffuse edema causes skin
to look like leather; concern exists for mast cell leukemia and organ involvement.
4. Telangiectasia macularis eruptiva perstons: minimal  in mast cells about dermal vessels; often no
Derier sign; tan macules that may have telangiectasias on trunk; middle aged adults;
most cells stain melachromatically (w/ Giesma and Toluidine blue)
7. Inflammatory Cutaneous Disorders
Ichthyosis: not really inflammatory; most are congenital/inherited
-X-linked is due to def. of steroid sulfatase and prevents normal skin shedding; Acquired ichthyosis may be paraneoplastic
Urticaria (Hives): allergic(Type I – IgE mediated hypersensitivity) and non-allergic forms exist
G: lesion is an edematous plaque that is called a “wheal”; usually w/ intense pruritus; usually gone w/in 24hrs; swelling of lip or
eyelid = “angioedema”
M: edema of the upper reticular dermis w/ minimal inflamm. infiltrate (if chronic may see eosinophils)
C: all wheels are not urticaria; vasculitis, bullous impetigo, etc. also present w. wheals
Dermatitis: 3 clinical presentations: 1. Acute = erythema, blisters, pruritus
2. Subacute = erythema, oozing, crustying, early scale formation, pruritus
3. Chronic = erythema, scaling, pruritus
- other dermatitis are on table 27-3 (p. 1195)
- allergic contact dermatitis is Type IV (cell mediated immunity); blisters are due to extreme spongiosis (intercellular edema) in epid.
Erythema Multiforme (EM): EM minor assoc. w/ herpes simplex;
EM major: Stevens Johnson Syn (SJS) – wide spread severe disease w/ mucus membrane involvment
and assoc. w/ allergic rxn to drugs or mycoplasma infxns (7-10 days)
Toxic Epidermal Necrolysis – explosive severe skin and mm damage w/ same causes
(overnight)
G: all three variants characterized by wheals, target lesions (true wheals w/ necrotic blistered center) and blisters; mm damage-major
M: minimal cellular (Lyc) infiltrate; vacuolar alteration along the BM zone; Dead keratinocytes in the epid. sometimes to the point
of full thickness epith. necrosis; similar histopathology occurs in GVHD and fixed drug eruption
Psoriasis: common scaling dermatosis; may be assoc. w/ arthritis; Variants include: classic plaque (mica-like silvery); guttate
(eruptive process w/ small scaly papules – assoc w/ strep pyogenes); erythrodermic (red scaly skin); pustular (pustules in red plaques);
pinpoint bleeding when scale is removed is Auspitz sign; nail dystrophies = 30% of patients
M: regular acanthosis w/o spongiosis; parakeratotic scale; collections of PMN’s in the epidermal living layer (spongiform pustule)
and stratum corneum (Munro’s microabscesses) are pathognomonic.
C: the Koebner phenomenonon = development of psoriasis at a site of non-specific trauma; psoriasis tend to be AD inheritance
Lichen Planus: pruritic self-limited but potentially protracted disorder of skin and mm
G: Violaceous papules (irregular, purple); fine grey-white lines on papules are called Wichham stria; mm has lacey white lesions
M: dense band-like lymphocytic infiltrate obscures dermal-epid. jn (DEJ); irregular (saw-tooth) rete ridges; dead keratocysts
(Civatte bodies) at DEJ; orthokeratotic hyperkeratosis
C: may be assoc. w/ Hep C; malignant degeneration (SCC) may develop in chronic mm lesions; Koebner pheno. (lines) may occur
Lupus Erythematosus: autoimmune connective tissue d/o; Localized (cutaneous) and multiorgan (SLE) forms exist
G: sharply demarcated hyperkeratotic lesions (DLE); can be widely spread mainly on malar eminences (sun-exposed) w/ SLE
M: superficial and deep periappendageal and pervascular lymphocytic infiltrate; vacuolar alteration along DEJ w/ BMZ thickening;
necrotic keratinocytes in epidermis; varying amounts of mucin; granular DEJ band of Ig and complement on direct IMF
C: positive lupus band on direct IMF; if band positive on non-sun exposed areas = more severe; ANA not pos. in skin-only cases
Bullous Diseases: many skin diseases have a blistering component, some characteristic depending on site of blister cleavage plane;
may be induced by autoimmune, friction, UVR, etc.
Pemphigous group of Disorders: group of blistering d/o that may affect skin or mm; blisters are intraepidermal w/ acantholysis;
due to antibodies to substances that hold cells together; several variants exist
1. Vulgaris (80%): due to antibody to Desmoglein 3 (adhesin); mm lesions often proceed skin lesions; flaccid blisters on trunk,
face, and prox. extremities; suprabasal blister; may become lethal
2. Foliaceous: endemic in S. America, but also sporadic cases; crusty (intact blisters rare); mm almost never involved
3. Vegetans: hyperplastic lesions in intertriginous areas (axilla & groin); oozing and crusting w/o obvious blistering
4. Erythematous: localized foliaceous; mainly on face; may be assoc. w/ SLE
M: all have pos. direct IMF – “net wire” pattern in epidermis on indirect; acantholytic keratinocytes float in blisters
Bullous Pemphigoid (BP): Sub-epidermal blisters; tense blisters; patients older; mm involvement rare; due to antibodies to BMZ
M: sub-epidermal blisters often contain eosinophils; fine BMZ band of complement and sometimes Ig
Dermatitis Herpetiformis (DH): a blistering disease assoc. w/ gluten sensitivity but only rarely w/ enteropathy (GSE)
G: grouped vesicles or erosions on an erythematous base on extensor surfaces; very pruritic
M: micro abscesses of PMN’s destroy dermal papillae; direct IMF shows granular deposits of IgA in dermal papillae
C: HLA-B8 and HLA-DRw3 are often assoc.
8. Non-inflammatory Blistering Diseases
Friction Blisters: common; subcorneal split; high heat and moisture are predisposing factors
Mechanobullous Disorders (Epidermolysis bullosa): diseases w/ genetic defects in elements nec. to hold skin together; several
variants; blister w/ minimal frictional trauma
Porphyria: due to genetic or acquired deficits in genes for enzymes,etc.; Porphyria Cutanea Tarda is the most common =
blistering and scarring w/ milial cyst formation in sun-exposed areas (esp. hands), hypertrichosis of temples (hair), often assoc. w/
hemochromatosis
9. Disorders of Epidermal Appendages
Acne Vulgaris: inflammatory d/o of sebaceous follicles; effects 80% of teenagers; initial lesions are non-inflamm. (comedomes); but
papules, pustules, nodules, cysts, and scarring may ensue
10. Panniculitis: inflamm. of fat lobules or fibrous connective tissue septae in sub cutis (often on legs)
Erythema Nodosum: really a “septitis” of unknown etiology commonly on skin; may be assoc. w/ strep., birth control pills,
sarcoid, TB, etc.; lesions somewhat painful but almost never drain thru skin surface
Erythema Induratum: more of an inflammation of fat lobules, commonly on post. legs; assoc. w. TB or unknown; may ulcerate
11. Infection and Infestation
Warts: benign keratinocyte neoplasms cause by HPV (esp. types 16, 18, 31, 33, 35 – assoc. w/ rare AR d/o called Epidermodysplasia
Verruciformis); several variants
1. Common: verrucous papules on most surfaces; may grow rapidly and bleed w/ minor trauma; show filiform epidermal
projections w/ parakeratosis, dilated papillary capillaries and areas of large keratohyaline granules; few koilocytes possible
2. Moist: occur on mm’s and in intertriginous areas; less verrucous; show a proliferation of keratinocytes w/ kocloyctosis
3. Flat: slightly raised; maybe hyperpigmented; legs and face are common; may be spread by scratching; show min. keratinocyte
proliferation w/ obvious koilocytosis
4. Plantar: often show massive keratohaline-like granules
Molluscum Contagiousum: caused by Pox virus (DNA); spread by physical contact and fomites
G: 2-4mm papules w/ central dell (opening to a hair follicle); may be much larger if immunosuppressed
M: can see cytoplasmic inclusion (molluscum bodies) in material expressed from lesion (35 microns); also present on biopsy
C: topical steroids may actually encourage spreading in patients w/ atopic dermatitis
Impetigo: Bullous from caused by Staph. aureus; group A Strep may also be present (erythema at edges of crusted lesion seen);
cutaneous strains of strep have been known to be nephritogenic also; Bullous form has acantholytic dermal cells, staph., and PMN’s in
a sub-corneal blister
Superficial Fungal Infections: 3 genera: Dermatophytes = Trichophyton, Epidermophyton, and Microsporum
-Onchomycosis = infxn of nails; but includes all genera not just these 3
-Tinea versicolor is caused by Malassezia furfur (hyper and hypo-pigmented patches on trunk)
-Fungal wall stains w/ PAS are usefuls (as is KOH)
Arthopod Bites, Stings, and Infestations (see book)
1. Pediculosis: louse infestation due to Head-capitis, Body-Vagabond’s disease, or Pubic-crabs; lice are blood feeders and bites
may become infected
2. Scabies (Sarcoptes scabiei var hominis): burrows in skin at stratum corneum; spreads by repeated physical contact; not a
blood feeder; intense pruritus due to type IV hypersensitivity to mite parts