DermatopathologyDermatopathologyKuliah-1 / Blok DMS

Dr H Soekimin SpPADr. H. Soekimin, SpPADr. T. Ibnu Alferraly, SpPADepartemen Patologi Anatomip gFK USU

Makroskopis Jaringan Kulit

Makula ( Macule ) : ruam bulat pada kulit, ukuran bervariasi, datar, perbedaan warna dgn kulit sekitar

Papula ( Papule ) : daerah kulit dgn elevasi solid Ø ≤ 5 mmPapula ( Papule ) : daerah kulit dgn elevasi solid Ø ≤ 5 mm

Nodul ( Nodule ) : daerah kulit dgn elevasi solid Ø ≥ 5 mm

Plak ( Plaque ) : daerah kulit dgn elevasi permukaan datar Ø ≥ 5 mmPlak ( Plaque ) : daerah kulit dgn elevasi, permukaan datar, Ø ≥ 5 mm

Vesikel ( Vesicle ) : daerah kulit yang berisi cairan, Ø ≤ 5 mm

Bula ( Bulla ) : vesikel besar Ø ≥ 5 mmBula ( Bulla ) : vesikel besar, Ø ≥ 5 mm

Blister : istilah untuk vesikel atau bula

f ( f )Likenifikasi ( Lichenification ) : penipisan daerah kulit, batas jelas, akbtpengikisan yg ber-ulang

Ekskoriasi ( Excoriation ) : - lesi akibat traumak k id i ( d h )- kerusakan epidermis ( deep scratch )

- sering ok ‘self-induced’

Papule: Raised dome shaped lesion less than 0.5 cm. (Common Nevi, Moles, Cherry angioma, Sarcoidosisy g

Plaque: A slightly raised area which is not very deep with a flat top and >0.5 cm . (Psoriasis)( )

Xanthelasma: Lipid deposits around the eyes.

Wheal: Firm, edematous (peau de orange) plaque. Evanescent and pruritic. (Hives)

Macule: A flat area of discoloration between 0 5 1 cm in size (freckles) bluishMacule: A flat area of discoloration, between 0.5-1 cm in size. (freckles), bluish macule (Mongolian spots).

Patch: Macule larger than 1 cm in size. Monocytic Leukemiaatc g y

Maculo-papular lesion: Characetristics of macule and papule. ( Sarcoidosis Malignant MelanomaHypereosinophilic syndrome Lymphoma )Hypereosinophilic syndrome, Lymphoma )

RashDesquamation

Striae: Prior stretch (pregnancy, loss of obesity, Gardner Diamond syndrome)

Excoriation: Infection (Scabies), primary skin disease (Eczema), Systemic disease (Hodgkin's disease, Liver disease)

Scale: Flake of flat horny cells which is loosened from the cells below (Psoriasis)

Crust: Dried serum, blood or superficial skin cells or a mixture of (Squamous cell cancer)

Scar: Reflects healing

Atrophy: Loss of substance of Skin. Thinning of epidermis, dermis or p y g p ,subcutaneous tissue. Ehler's Danlos syndrome

Lichenification: Thickened skin with increased skin markings (Lichen simplex chronicus)

Keloid: Exuberant scar formation

Vescicle: Dome shaped, thin wall, less than 05.cm in diameter, filled with fluid (Leukemia cutis)

Pustule: Vescicle filled with pus. Less than 0.5 cm in size. (Acne pustule)

Blister: Vesicle larger than 0.5 cm

Bullae: Gas gangrene.

Cyst: Deeply seated fluid (pus blood or fluid) filled cavity < 0 5 cm in sizeCyst: Deeply seated fluid (pus, blood or fluid) filled cavity. < 0.5 cm in size. Fluctuation present.

Fissure: Leniar cleavage in skin. Dermis exposed, hence painful.

Ulcer: Hole in skin. Heals with scar when it is not malignant. (Squamous cell cancer)

E ti L d h lErotion: Less deeper than ulcer

Telangiectasia: a small spidery superficial vascular lesions. Blanches with pressure. (normal in children and women. Liver disease)

Petechiae: Extravasation of blood. Does not blanch with pressure. <0.5 mm

Vesicle/ Bullae

Clinical findings of the proband. (a) Confluent vesicles and bullae on the palms d l t l t th fi (b) D ti th l ( ) C fl tand lateral aspects on the fingers. (b) Desquamation on the palms. (c) Confluent

vesicles on the sole. (d) Histological results showing spongiosis and spongiotic vesicles (hematoxylin and eosin staining).

Purpura

FiFisure

Fissure (fish Your), Erosion, And Ulcer

A fissure is a thin but deep linear split in the epidermis that e tendsepidermis that extends into the dermis. Severe dry skin can have fissures. An erosion is a depressed lesion that isdepressed lesion that is wider than a fissure but not as deep. An erosion, which is usually moist, may result from amay result from a ruptured vesicle or bulla. An ulcer is a deep erosion in which all of the epidermis and part of theepidermis and part of the dermis are eaten away (eroded). A bed sore is an ulcer. Ulcers often leave scarsleave scars.

MaculaMacula

Telengiectasig

Ulcer

Mikroskopis Jaringan Kulit

AKANTOLISIS :

The loss of cohesion between epidermal or adnexal keratinocytes

Example of acantholysis in Pemphigus Foliaceus

AKANTOSIS

The increase in the thickness of the stratum malpighii

Examples of acanthosis in Psoriasis

Lichen Simplex Chronicus

Acanthosis Nigricans: Velvety appearing hyperpigmented skinAcanthosis Nigricans: Velvety appearing, hyperpigmented skin. Associated with diabetes and a number of other disorders. Multiple skin tags also seen in this picture of the axillary region.

ANAPLASIA

The atypical appearance of nuclei as is found in malignant neoplasia. Anaplastic nuclei are usually large, irregular and hyperchromatic, and may produce bizarre or atypical mitotic figures.

APOPTOSIS

The dropping off of colloid bodies from the epidermis into the dermis. Apoptosis typically occurs in disorders in which basal cell damage occurs, such as lichenoid tissue reactionslichenoid tissue reactions

Lichen Plannus

Benign Lichenoid Keratosis

BULLA

A cavity of at least 5 mm in diameter forming within or below the epidermis

Example is a sub-epidermal bulla in Epidermolysis Bullosa

EPIDERMOLITIK HIPERKERATOSIS

Also called granular degeneration. It is characterized by:

1. Peri-nuclear clear spaces in the upper stratum malpighii p pp p g2. Indistinct cellular boundaries 3. A markedly thickened granular layer with increased numbers of keratohyalin 4. Granules and hyperkeratosis

Actinic Keratoses

1.Acantholysis, 2. Hyperkeratosis, 3. Parakeratosis

Hypergranulosis is the most prominent feature in this case.case.

E P I T H E L O I D

Cells derived from macrophages, seen in granulomas and characterized by a large,usually oval, pale, vesicular nucleus with a clearly visible nuclear membrane. The cytoplasm is abundant ill-defined and slightly eosinophilicThe cytoplasm is abundant, ill defined and slightly eosinophilic.Multinucleated epithelioid or giant cells arise from mature macrophages that fuse rather than divide. Langhans giant cells have nuclei in a semicircle at the cell periphery. Foreign body giant cells have nuclei distributed randomly.

GIANT CELL

Large multinucleated cells. Epidermal multinucleated giant cells are characteristic of herpes virus infections. Histiocytic giant cells whose nuclei form a horseshoe arrangement are calledLanghans type giant cells. Touton type giant cells have a ring of nuclei surrounding foamy cytoplasm with cytoplasm usually also visible around the nuclei. Foreign-body giant cells have a haphazard nuclear arrangementForeign-body giant cells have a haphazard nuclear arrangement

PARAKERATOSIS

Retention of nuclei in the stratum corneum. This is a normal finding on mucous membranes

P L E O M O R F I K

The variation in the appearance of the nuclei of the same cell type. If pronounced and associated with large, irregular, hyperchromatic nuclei it is termed anaplasia and is often an indication of malignancy.

V I L L U S

A dermal papilla extending into a bulla, vesicle, or lacuna which is covered with a single layer of epidermal cells resulting from suprabasalar acantholysis .Example of Villus in Pemphigus vulgaris

REAKSI UMUM KULIT TERHADAP JEJAS (i j )REAKSI UMUM KULIT TERHADAP JEJAS (injury)

• Inflamasi Akut : dermis + epidermis ; kemerahan, panas, bengkak, sakit p ; , p , g ,

• Penumpukan cairan antara keratinosit : SpongiosisSpongiosis yg hebat : Vesikel ( penumpukan cairan terlokalisir )

• Pembengkakan dermis : elevasi epidermis ( wheal formation )

• Jejas berat : kulit Nekrosis Epdermis Nekrosis : UlcerasiDermis Nekrosis : gmbrn klinis beragam, tgtng struktur yg terlibat

Inflamasi Kronis :Inflamasi Kronis :- Penebalan epidermis : ACANTHOSIS- penebalan Staratum Corneum : HYPERKERATOSIS- Fibrosis dermis

Inflamasi Kulit Akut

- Terjadi dalam hitungan hari – minggu

- Mikroskopis : sel2 mononuklear ( PMN ), neutrofil ( jarang ), oedem,jejas pada : epidermis, pembuluh darah, sub-kutan

- Dapat berlanjut : kronis

Inflamasi Kulit KronisInflamasi Kulit Kronis

Inflamasi Kulit AkutUrticaria • Skin lesions and pruritus occur, caused by an allergic or nonallergic mechanism.

• Histamine is thought to be the most important biochemical mediator in urticaria.

• Mast cells are the major histamine-releasing cells of the skin. j gThe mast cell possesses high-affinity receptors for immunoglobulin E (IgE). In allergic reactions, adjacent IgE molecules, which are bound to the surface of mast cells by the high-affinity IgE receptors, are cross-linked by allergens, leading to the release of histamine and other mediatorsto the release of histamine and other mediators.

• Basophils also possess the high-affinity IgE receptor and may be involved in urticaria.

• Other inflammatory cells (ie, vide infra) are recruited into the lesional area in urticaria, particularly in chronic urticaria. These cells can release cytokines and chemokines that can cause histamine release or otherwise contribute to thechemokines that can cause histamine release or otherwise contribute to the pathology.

• A lymphocytic infiltrate is commonly found in the lesions of both acute and chronic types of urticaria.

• Some urticarial lesions have a mixed cellular infiltrate, ie, a mixture of lymphocytes, polymorphonuclear leukocytes (PMNs), and other inflammatory cells.

• This mixed type of infiltrate seems to be particularly characteristic of certain refractory forms of chronic urticaria, such as autoimmune-mediated urticaria.

• The mixed infiltrate is similar to the histopathology of the allergic late-phaseThe mixed infiltrate is similar to the histopathology of the allergic late phase response.

• Some patients with particularly severe or atypical urticaria are found to h li i ki bihave vasculitis on skin biopsy. Indeed, a spectrum in histopathology seems to exist, ranging from lymphocytic to vasculitic, that correlates approximately with disease severity, from mild to severe.

Eczematous Dermatitis Acute

• Eczema : clinical term, embrace many conditions, many underlying causes

• Early stage : red, papulovesiculer, oozing, crusted lesionsIf persistence : Scaling Plaques (+)

• Classification : - Allergic contact- Atopic- Drug Related Eczematous

Photoeczematous- Photoeczematous- Primary irritant forms

Histologic sections of skin show epidermal acanthosis with marked spongiosis

Eczema Dermatitis

Histologic sections of skin show epidermal acanthosis with marked spongiosis, leading to intraepidermal vesicle formation. The vesicles are filled with serum and inflammatory cells.

EczemaEczema Dermatitis

A higher power view reveals the nature of the infiltrate. Associated with the spongiosis and vesicle formation are numerous eosinophils andAssociated with the spongiosis and vesicle formation are numerous eosinophils and scattered neutrophils

Erythema Multiformis

• Erythema multiforme (EM) is an acute self-limited eruption characterized by a distinctive clinical eruption, the hallmark of which is the iris or target lesion.

• EM may present within a wide spectrum of severity• EM may present within a wide spectrum of severity.

• EM minor represents a localized eruption of the skin with mild or no mucosal involvement, corresponding to the initial description of von Hebra.

• EM major and Stevens-Johnson syndrome (SJS) are more severe mucosal and skin diseases and are potentially life-threatening disorders.

Erythema Multiformis

• The early lesion of EM is characterized by infiltration of lymphocytes at the dermal-epidermal interface with accompanying exocytosis and spongiosis in the epidermis.

• Individual eosinophilic necroticIndividual eosinophilic necrotic keratinocytes may be scattered and surrounded by lymphocytes (satellite cell necrosis).

• The dermal changes include edematous papillary dermis, ectatic and swollen endothelial cells ofectatic and swollen endothelial cells of the vessels, and extravasation of the red blood cells.

Inflamasi Kulit KronisPsoriasis

• Psoriasis is a skin disease that causes itchy or sore patches of thick, red skin with silvery scales.

• Psoriasis is a common, chronic, relapsing, inflammatory skin disorder with a strong genetic basisgenetic basis

• Usually lesions on elbows, knees, scalp, back, face, palms and feet, but they can show up on other parts of body.

• A problem with immune system causes psoriasis. In a process called cell turnover, skin cells that grow deep in the skin rise to the surface. Normally, this takes a month. In psoriasis, it happens in just days because your cells y p pp j y yrise too fast.

• Psoriasis can last a long time, even a lifetime. Symptoms come and go.

Psoriasis

Psoriasis

Epidermis• Mitotic activity of basal keratinocytes is increased almost 50-fold, with

keratinocytes migrating from the basal to the cornified layers in only 3 5 dayskeratinocytes migrating from the basal to the cornified layers in only 3-5 days compared to the normal 28-30 days.

• With hyperproliferation of skin cells, the epidermis becomes thickened or acanthotic in appearance and an increase in size of the rete ridges is observed.

• Abnormal keratinocyte differentiation is noted throughout the psoriatic plaques, as manifested by the loss of the granular layeras manifested by the loss of the granular layer.

• The stratum corneum is also thickened, and the retention of cell nuclei in this layer is referred to as parakeratosis.

• Neutrophils and lymphocytes can be observed migrating upwards from the dermis into the acanthotic epidermis. Neutrophils may form localized collections known as Munro microabscesses The presence of alternating collections ofknown as Munro microabscesses. The presence of alternating collections of neutrophils sandwiched between layers of parakeratotic stratum corneum is virtually pathognomonic for psoriasis.

Munro microabscesses are composed of degenerated polymorphonuclearMunro microabscesses are composed of degenerated polymorphonuclear leukocytes (PMN's) in the horny layer (stratum corneum) and are seen in psoriasis and seborrheic dermatitis

PsoriasisDermis

• Marked hypervascularity and an increase in the size of the dermal papillae occurpapillae occur.

• An activated CD3+ lymphocytic infiltrate is noted around blood vessels, with T cells expressing cutaneous lymphocyte–associated antigen, co-stimulatory molecules such as CD2, and LFA-1 adhesion molecules.

• An aggregation of neutrophils in the dermis occurs that extends up into the epidermis.epidermis.

Lichen Planus

• LP is a cell-mediated immune response of unknown origin• LP is a cell-mediated immune response of unknown origin.

• LP may be found with other diseases of altered immunity; these conditions include ulcerative colitis, alopecia areata, vitiligo, dermatomyositis, morphea, lichen sclerosis, and myasthenia gravis.

• An association is noted between LP and hepatitis C virus infection, chronic active hepatitis and primary biliary cirrhosishepatitis, and primary biliary cirrhosis

The histopathologic features distinguish LP based on the presence of irregularThe histopathologic features distinguish LP based on the presence of irregular acanthosis and colloid bodies in the epidermis with liquefactive degenerationand linear fibrin deposition in the basal layer. The upper dermis has a bandlike infiltrate of lymphocytes and histiocytes.

Lichen Planus

The inflammatory reaction pattern is characteristic. The epidermis is hyperkeratotic with irregular acanthosis and focal thickening in the granular layerthe granular layer.

Degenerative keratinocytes, known as colloid or Civatte bodies, are found in the lower epidermis. In addition to apoptotic keratinocytes, colloid bodies are composed of globular deposits of IgM (occasionally immunoglobulin G [IgG] or immunoglobulin A [IgA]) and complement.

Linear or shaggy deposits of fibrin and fibrinogen and liquefaction are in the basement membrane zone.

Lichen Planus

Lichen Simplex Chronicus• LSC is found on the skin in regions accessible to scratching.

Pruritus provokes rubbing that produces clinical lesions, but the underlying pathophysiology is unknown.

• Some skin types are more prone to lichenification, such as skin that tends toward eczematous conditions (ie, atopic dermatitis, atopic diathesis).

• A relationship likely exists between central and peripheral neural tissue and inflammatory cell products in the perception of itch and ensuing changes in LSC.

• The possible interplay among primary lesions psychic factors and the intensity of• The possible interplay among primary lesions, psychic factors, and the intensity of pruritus additively influence the extent and severity of LSC.

• Histologic examination demonstrates hyperkeratosis, acanthosis, spongiosis, and patches of parakeratosis in the epidermis.

• Epidermal thickening of all layers is noted, with elongation of rete ridges and with pseudoepitheliomatous hyperplasia. Papillary dermal fibrosis with vertical streaking of collagen bundles is characteristic.

• A characteristic finding of LSC that is noted on electron microscopy is frequent collagen fibers attached to and just above the lamina basalis