PATHOLOGY OF THE SKIN

dr. Tamás Székely S.E. 2nd. Department of Pathology 2017 Pathology of the Skin

• Organpathology in general • Special aspects of the skin pathology • Clinical correlation • „Life of lesions” • Diagnostic and therapeutic considerations Organpathology • Developmental disorders, • Ichthyosis Inherited- and genetical alterations • Degenerative and metabolic • Xanthomata, porphyria, disease gout, myxoedema

• Circulatory disorders • Vasculitides, DM

• Inflammation (Acute- • Urticaria, Psoriasis Chronic): Non-infective • Infections • Basal cell carcinoma, • Neoplasias Squamous cell carcinoma, Melanoma Malignum Special aspects of the skin pathology

• Visible organ: Almost all speciality meets with; esthetical problem • UV irradiation: aging, D3-vitamin, carcinogenesis • Limited number of reaction patterns • Differential diagnostics requires close clinico- pathological cooperation • Special regions: oral mucosa, anogenital region, nail- and nailbed, alopecia, conjuctiva Limited number of reactions

Eg.: Eczematous (spongiform)dermatitis:

Irritative contact dermatitis Allergic contact dermatitis Atopic dermatitis Drug reaction Pityriasis rosea Etc. Pathology of the Skin

I. Basic terms, primary lesions II. Dermatitides, Infections III. Manifestations of systemic diseases IV. Tumors of the surface epithelium and skin appendiges V. Nevus pigmentosus and melanoma malignum. VI. Mesenchymal tumors Anatomy Primary Lesions • Macule Circumscribed lesion, 5 mm or smaller in diameter, characterized by flatness and distinguished by coloration (Patch is greater than 5 mm) • Papule Elevated dome-shaped or flat-topped lesion 5 mm or less across (nodule is greater than 5 mm) • Plaque Elevated flat-topped lesion, usually greater than 5 mm across (may be caused by coalescent papules) • Pustule Discrete, pus-filled, raised lesion • Vesicle Fluid-filled raised lesion 5 mm or less across (Bulla is greater than 5 mm. Blister is the common term for either.) • Wheal Itchy, transient, elevated lesion with variable blanching and erythema formed as the result of dermal edema • Onycholysis Separation of nail plate from nail bed

• Scale Dry, horny, platelike excrescence; usually the result of imperfect cornification • Excoriation Traumatic lesion breaking the epidermis and causing a raw linear area (i.e., deep scratch); often self-induced • Lichenification Thickened and rough skin characterized by prominent skin markings (as lichen on a tree trunk); usually the result of repeated rubbing Secondary Lesions

Modification of a primary lesion that results from traumatic injury, evolution from the primary lesion, or other external factors.

Subepidermal Blister Ulcus Microscopic terms

• Acantholysis: Loss of intercellular cohesion between keratinocytes • Acanthosis Diffuse epidermal hyperplasia • Dyskeratosis Abnormal, premature keratinization within cells below the stratum granulosum • Erosion Discontinuity of the skin showing incomplete loss of the epidermis • Exocytosis Infiltration of the epidermis by inflammatory cells • Hydropic swelling (ballooning) Intracellular edema of keratinocytes, often seen in viral infections • Hypergranulosis Hyperplasia of the stratum granulosum, often due to intense rubbing • Hyperkeratosis Thickening of the stratum corneum, often associated with a qualitative abnormality of the keratin • Lentiginous A linear pattern of melanocyte proliferation within the epidermal basal cell layer • Papillomatosis Surface elevation caused by hyperplasia and enlargement of contiguous dermal papillae • Parakeratosis Keratinization with retained nuclei in the stratum corneum. On mucous membranes, parakeratosis is normal. • Spongiosis Intercellular edema of the epidermis • Ulceration Discontinuity of the skin showing complete loss of the epidermis revealing dermis or subcutis dyskeratocyte parakeratosis hypergranulosis acanthosis

papillomatosis Hydropic swelling ulceration spongiosis Infections (very few examples) Bacterial: • impetigo, erysipelas, folliculitis, lyme, tuberculosis, syphilis

Viral: • Common wart, condyloma acuminatum, herpes simplex, herpes zoster, molluscum contagiosum

Fungal: • tinea corporis, tinea versicolor

Parasitic Verruca Vulgaris ( Common wart)

HPV: 1,2,4,7, 26-29 Condyloma Acuminatum HPV 6, 11

S.E. Bőr-, Nemikórtani és Bőronkológiai Klinika archivumából Herpes Zoster (varicella zoster virus)

chickenpox

S.E. Bőr-, Nemikórtani és Bőronkológiai Klinika archivumából Demodex folliculorum Manifestations of systemic diseases

Skin lesions associated with cancer 1. Paraneoplastic syndromes 2. Inherited carcinoma syndromes 3. Cutanous metastasis of internal organ cancers

Systemic autoimmune diseases SLE, SDLE, Dermatomyositis, Scleroderma

Diabetes Mellitus

Drug erruptions Obligatory paraneoplasias

• Acanthosis nigricans maligna • Acrokeratosis paraneoplastica Bazex • Erythema gyratum repens (Gammel- syndrome) • Hypertrichosis lanuginosa acquisita. • Erythema necroticum migrans (glucagonoma syndrome) Facultative paraneoplastic syndromes • Dermatomyositis • Thrombophlebitis migrans (Trousseau sign) • Sweet syndrome (acute febrile neutrophil dermatosis) • Paraneoplastic pemphigus • Aquired ichthyosis • Extramammary Paget • Florid cutan papillomatosis • Keratoderma palmoplantare acquisita diffusa • Leser-Trélat syndrome • Hypertrophic osteoarthropathia • Multicentric reticulohistiocytosis • Carcinoid syndrome • Generalized pruritus Florid papillomatosis Acanthosis nigricans

Dr. Tóth Jeanette archívumából

S.E. Bőr-, Nemikórtani és Bőronkológiai Klinika archivumából Scleroderma „Diabetic leg”

Ulceration, impaired wound healing, phlegmonous inflammation due to micro- and macroangiopathy

S.E. Bőr-, Nemikórtani és Bőronkológiai Klinika archivumából Drug eruptions

• Urticaria • Morbilliform • Fixed drug eruption • Erythema multiforme • Stevens-Johnson Syndrome • Toxic epidermal necrolysis Dermatitides

• More than thousands of clinical entities

• Acute- Chronic

• Epithelial changes

• Pattern and components of the inflammation Analysis of dermatitides

Pattern and component of Epithelial changes inflammation • Hyperplasia • Lichenoid • Atrophy • Superficial and/or deep • Papillomatosis perivascular lymphocytic • Spongiosis • Perifollicular • Psoriasiform hyperplasia • Granulomatosus • Vacuolar • Vasculitides • Vesiculo-bullous change • Subcutanous: Panniculitis Superficial perivascular infiltration Psoriasiform hyperplasia

Subepidermal blister granuloma Dermatitis (see textbook)

Acute • Urticaria • Acute eczematosus dermatitis • Erythema multiforme

Chronic: • Psoriasis • Lichen ruber planus Urticaria ( Wheal)

S.E. Bőr-, Nemikórtani és Bőronkológiai Klinika archivumából Psoriasis Vesiculo- bullous dermatitides

Antibodies against demosomes- hemidesmosomes ( desmoglein 1, -3 proteins)

ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE, 8/E

Pemphigus foliaceus pemphigus vulgaris bullous pemphigoid derm. herpetiformis

Antibodies highlighted by direct Local intraepidermal deposition…..IgG, IgM immunfluorescence method Pemhigus Vulgaris Neoplasia

• Tumors of the surface epithelium • Tumors of the skin appendiges • Melanocytic lesions • Mesenchymal neoplasias • Lymphomas • Metastasis Epidermal tumors Seborrheic Keratosis • Confluent sheets of small, basaloid cells • Surrounding keratin pseudocysts • Basal hyperpigmentation • No atypia Seborrheic keratosis variants

Irritated Verrucosus

Reticular-adenoid

Clonal Leser-Trélat sign

S.E. Bőr-, Nemikórtani és Bőronkológiai Klinika archivumából Solar (actinic) damage Basal cell carcinoma

Most common malignancy (high incidence, very low mortality)

Semimalignant: Locally infiltrative and destructive, but never gives distant metastasis

Occurs on sun- exposed skin Carcinoma basocellulare Carcinoma basocellulare

Retraction artifact Variants of BCC

Nodular-cystic

Multicentric-superficial

Infiltrative Squamous cell carcinoma Pigmented Nevi (Mole)

• Pigmentált nevus Life of nevi junctional compound dermal Nevus pigmentosus

symmetry

„maturation” Halo nevus

S.E. Bőr-, Nemikórtani és Bőronkológiai Klinika archivumából Spitz nevus Nevus dysplasticus Other variants of nevi

Blue nevus Deep-penetrating nevus

Osteonevus of Nanta Halo nevus Melanoma Malignum

A: asymetry B: border C: colour D: diameter E: elevation

+ itching Spontanous bleeding

~75% de novo, 25% in naevus

S.E. Bőr-, Nemikórtani és Bőronkológiai Klinika archivumából Melanoma Malignum

asymmetry Pagetoid spread TIL Dermal mitotic activity Progression of Melanoma Malignum

•Superficial-spreading melanoma (SSM) Horizontal phase

•Nodular melanoma

•Acral-Lentiginous Melanoma Vertical phase

•Lentigo Maligna Stage

Clark level Breslow thickness I. in mm II. III. IV.

V. Prognostic factors

• Type (SSM, LM, ALM, NM) • Breslow, Clark, pTNM • Cell type (epitheloid, spindle) • Vascular invasion, perineural spreading • Mitotic rate (dermal mitosis/mm2) • Satellite • Regression • Tumor infiltrating lymphocytes (TIL) • Nevus • Ulceration • Sex, Localization Melanoma Malignum

Dr. Tóth Jeanette archivumából

Merkel cell carcinoma

Primary neuroendocrine carcinoma of the skin Mesenchymal tumors

• Fibrous-fibrihistiocytic: Dermatofibroma • Fibroblastic • Lipomatous: Lipoma • Angiogenic: Hemangioma, Kaposi sarcoma, angiosarcoma • Smooth muscle: pilar leiomyoma • Periferal nerve, nerve seath: NF, Swannoma Dermatofibroma Neurofibroma Lipoma fibroblastic

hemangioma Leiomyogenic