SURGICAL PATHOLOGY: DISEASES OF THE SKIN Dr. Christine Ayochok | August 19, 2015

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[5] TUMORS OF CELLULAR MIGRANTS TO THE SKIN Lymphocytes and Mast cells

T-cells MYCOSIS FUNGOIDES/CUTANEOUS T-CELL LYMPHOMA o Primary T-cell lymphoma of the skin o Tumor cells: clonal populations of CD4 subset (T helper)o Marker: CLA (common lymphocytes antigen: CD45)o Specific abnormalities

Aberrant cell surface Ags Clonal T-cell receptor rearrangement

o Usually localized to the skino Occasionally: systemic involvement o Prognostic factors

% of body surface involved Degree of progression from patch to plaque to nodular forms

o Some patients: seeding of blood by tumor cells, with erythema and scaling (diffused) Sezary syndrome: disseminated mycosis fungoides

Plaque stage (stage 2)

SEZARY-LUTZNER CELLS o Hallmark of CTCL o CD4+ T-cells in band-like aggregates o Superficial dermis o Invade epidermis singly or in clusters (Pautrier microabscesses): initially

Misnomer: since the microabscess is not made of neutrophils but tumor cells o Advanced disease: into the dermis

Probably patch stage

Start of microabscess formation Pautrier microabscess

First: Patch stage Second: Plaque stage Third: Nodular/ Tumor stage Fourth: Seeding into the blood, erythematous scales [Sezary syndrome]

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Mast cells MASTOCYTOSIS o Increase # of mast cells in skin o Acquired activating point mutations of tyrosine

kinase (c-Kit receptor) Promotes mast cell growth, survival

Urticaria pigmentosa o Localized form o Typically in children o Usually multiple lesions: papules, plaques o Maybe single (solitary mastocytoma): nodules o Occasionally: systemic disease - liver, spleen, BM, LN

o Symptoms

Related to effects of substances released from degranulation of mast cells

Granules: histamine, heparin

o Darier sign: edema and erythema after skin lesion is rubbed Nonspecific

o Dermatographism

Dermal edema in normal skin after stroking with a pointed instrument

o Increase # of mast cells in the dermis o Use of special stains: toluidine blue,

Giemsa o Mast cell tryptase: helpful when mast

cells are already degranulated o Epidermis is normal

Solitary mastocytosis

Urticaria pigmentosa presenting as multiple plaques

SURGICAL PATHOLOGY: DISEASES OF THE SKIN Dr. Christine Ayochok | August 19, 2015

Normal epidermis

Bone marrow: systemic mastocytosis

Upper Left: Special stain with toluidine blue Arrows pointing to granules Upper right: BM toluidine blue (systemic mastocytosis) Lower left: Liver toluidine blue (systemic mastocytosis)

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SKIN DISEASES

ICHTHYOSIS o Chronic, excessive keratin buildup (hyperkeratosis): fish-like scales

Some cases: due to defective desquamation o X-linked form: deficiency of steroid sulfatase - accumulation of cholesterol sulfate

Promote compaction and aggregation of S. corneum cells o Autosomal dominant or recessive o Compacted, thickened stratum corneum (hyperkeratosis) o Loss of normal basket-weave pattern

Can be compounded by bacterial infection

SURGICAL PATHOLOGY: DISEASES OF THE SKIN Dr. Christine Ayochok | August 19, 2015

[6] ACUTE INFLAMMATORY DERMATOSES

o Last from days to weeks Vs. chronic: months to years

o Lymphocytes and macrophages o Edema

URTICARIA o Localized mast cell degranulation leading to dermal microvascular hyperpermeability

(edema)o Forms

IgE-dependent: Ag exposure IgE-dependent: drugs, chemical Complement-mediated: Hereditary angioneurotic edema (HAE): C1 deficiency

o Basic lesions: wheals Papules to plaques

Papules Wheal HISTOLOGY o Widely spaced collagen bundles due to dermal edema o Dilated lymphatic channels: lymphangiectasia o Epidermis is normal

ACUTE ECZEMATOUS DERMATITIS o Eczema: blistering disease o Papulovesicular, oozing, red, crusted lesions o Progress to scaling plaques due to acanthosis and hyperkeratosis o Categories based on initiating factors

Allergic contact dermatitis Atopic dermatitis Drug-related Photoeczematous Primary irritant

o Ag taken by Langerhans cells o Presented to CD4+ T-cells: effector and memory T cells o Re-exposure to Ag: memory T-cells go to site - release cytokines and chemokines o Hallmark: spongiosis - edema in the epidermis

”Spongiotic dermatitis” o When edema is severe may lead to intraepidermal vesicles

center VARIANTS: STEVENS JOHNSON SYNDROME o Erosions, hemorrhagic crusts o Confined to lips and oral mucosa o Secondary bacterial infections: sepsis TOXIC EPIDERMAL NECROLYSIS (TEN) o Diffuse necrosis o Sloughing of cutaneous/mucosal epithelial surfaces o Hallmark: interface dermatitis

Dermal edema Lymphocytes at the DEJ Dying/dead keratinocytes

o Progression: lymphocytes go up to epidermis o Blister formation in the epidermis due to necrosis o With necrosis of keratinocytes: formation of intraepidermal vesicles

Oozing stage (multiple blisters) Erythematous blistering lesions Plaque stage

Green: Inflammatory response Blue: spongiosis

Arrows: intraepidermal vesicles

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SURGICAL PATHOLOGY: DISEASES OF THE SKIN Dr. Christine Ayochok | August 19, 20154

ERYTHEMA MULTIFORME o HSR to infections or drugs o Associated with:

Infections: herpes, typhoid, leprosy Drugs: PCN, sulfonamides Malignancy: carcinoma, lymphoma Collagen vascular disease: lupus and polyarteritis nodosa (PAN)

o Immune-mediated epidermal cell injury Cell death by CD8+ T-cells (central part of lesion) and CD4+ T-cells and Langerhans cells at the erythematous periphery

o “Multiform” lesions: macules, papules, bullae, vesicles

o Target lesion: red macule/papule with pale or eroded Target lesions

Left: Stevens Johnson Syndrome

Right: TEN

DDx: Burn

Red: Dean keratinocyte Green: Inflammatory infiltrate

Blue: DEJ

Formation of intraepidermal vesicles because of necrosis