HISTOPATOLOGI LESI VESIKULOBULOSA DAN KEGANASAN

 

• Lesi vesikubulosa

  • Vessicle-Bulla

    • A clear fluid lesion just below the epithelium which ruptures to form an ulcer
    • Smaller than 5mm 🡪VESICLE
    • Larger than 5mm 🡪 BULLA

  • Manifest in the skin and mucous membranes

  • appearance of blisters and secondary erosions.

  • Bullous autoimmune dermatoses

    binding of autoantibodies to specific adhesion molecules in epidermal desmosomes and in some cases in the area of the dermo epidermal basement membrane zone. The binding of circulating autoantibodies and the induction of an inflammatory reaction in the area of target structures lead to loss of adhesion with subsequent intra or subepidermal blister formation

  • Istilah Umum

    • SPONGIOSIS:

      accumulation of extracellular fluid within epidermis with resultant separation of keratinocytes (eczematous dermatitis, allergic contact dermatitis, miliaria)

    • ACANTHOLYSIS:

      loss of appropriate keratinocyte cell-cell contact (pemphigus, acantholytic dermatosis, irritant dermatitis)

    • RETICULAR DEGENERATION:

      Ballooning degeneration with secondary rupture and death of the keratinocytes (viral, eczematous dermatitis)

    • CYTOLYSIS

      disruption of keratinocytes due to friction or heat (EB simplex, epidermolytic hyperkeratosis, friction blister)

    • Basement membrane zone disruption or destruction from primary structural deficiencies, humoral and cellular immunologic damage (bullous pemphigoid, cicatricial pemphigoid, linear IgA, dermatitis herpetiformis, epidermolysis bullosa acquisita, junctional epidermolysis bullosa, epidermolysis bullosa dystrophica)

• PEMPHIGUS VULGARIS

  • Autoimmune disease

  • CLINICAL FEATURES

    • Painful ulcers or bulla are formed.
    • formed any where in the oral cavity
    • The bulla is rapidly ruptured leaving a collapsed roof of grayish membrane with a red ulcerated base. The ulcer may look like an apthous ulcer or may be large map shaped
    • Nikolsky sign is positive
    • involve skin, oesophagus, cervix

    

    

  • Pathogenesis

    • There are circulating antibodies of type IgG.
    • These antibodies are reactive against the desmosomes or the tonofilament complex
    • There destruction or disruption of these tonofilament complex 🡪 loss of tonofilament complex 🡪 loss of attachment from cell to cell

  • Histopathology

    • Intra epithelial vesicles or bulla are produced by acantolysis
    • These changes are in the stratum spinosum or the prickle cell layer
    • eosinophils may be seen

    

    

    These cell loose there polyhedral morphology rather they are small rounded and contain hyper chromatic nuclei called the TZANK CELLS

• Pemphigoid

  • Autoimmune

    • Mucous membrane pemphigoid\
    • Bullous pemphigoid

  • Gambaran Klinis

    • Blisters may arise on erythematous and on normal skin and may be associated with dermal edema.
    • The blisters are tense and dome shaped, obtaining a diameter of many centimeteres.
    • The blisters are tough and may remain intact for several days, the contents often becoming jelly-like with coagulated fibrin.
    • Mucosal lesions occur less frequently and are less severe than in pemphigus vulgaris and are usually confined to the mouth.

  • Pathogenesis

    • Antibody antigen complex
    • Complement activation
    • Neutrophils & Eosinophils recruited
    • Release of proteases by the recruited cells
    • Sub epithelial blister formation

    

  • HPA

    

• Erythema Multiform

  • Definisi

    acute mucocutaneus hypersensitivity reaction of the skin and mucous membrane that causes a variety of skin lesion → Multiform

  • Type

    • erythema multiform minor
    • Erythema multiform mayor
    • Steven Johnson Syndrome
    • Toxic Epidermal Necrolysis
    • Herpes associated erythema multiform

  • ETIOLOGY

    • Immune mediated disease 🡪 depositition of immune complexs in superficial microvasculature of skin n mucous membrane
    • Drug (sulfonamide, phenylbutazone, trimethropin)
    • Microorganism (HSV, Mycoplasma pneumoni)
    • Vaccination, radiation therapy, crohn’s disease, ulcerative colitis

  • CLINICAL FEATURES

    • Acute/explosive onset with fever and malaise

    • Macule/papule, 0,5-2cm, segmental distribution

    • Conjunctivitis

    • Lips grossly swollen, split crusted bleeding

    • BULL’S EYE

      Consist of central bulla/pale clearing area, surrounded by edema an band of erythema 🡪 concentric ring like appearance

      

  • ORAL MANIFESTATION

    • Lips is prominently involved followed by buccal mucosa, palate, tongue and face
    • Oral lesion start by bullae, on a arythematous base and break rapidly into irregular ulcers
    • Lesions are larger, irregular, deeper and often bleed
    • Sloughing of mucosa and diffuse redness with bright red raw surface
    • Healing 🡪 2 weeks

    

  • Histopathological

    • Intracellular edema of the spinous layer of epithelium and edema of superficial connetive tissue 🡪 subepidermal vesicle
    • Liquefaction degeneration in the upper layer of epithelium with intraepithelial vesicle formation and thinning
    • Dilatation of the superficial cappilaries and lymphatics in the upper most layer of the connetive tissue is prominent and infiltrate numerous eosinophils
    • Necrotic eosinophilic keratinocytes are seen in the blister area

    

• STEVEN JOHNSON SYNDROM

  • SEVERE FORM of Erythema Multiforme with tippically involved

  • 🡪 skin, oral cavity, eyes and genetalia

  • Fever, malaise, photophobia, eruptions on oral mucosa, genital mucosa and skin

  • Lesion

    • CUTANEOUS LESION 🡪 similar to erythema multiforme
    • EYE LESIONS 🡪 photophobia, conjunctivitis, cornea ulceration
    • GENITAL LESIONS 🡪 non specific urethritis, balanitis and vagina ulcers
    • COMPLICATION 🡪 traceo-bronchial ulceration and pneumonia

  • ORAL MANIFESTATION

    • Extremely painful
    • Mucosal vesicles/bullae occur, rupture and leave a surface covered with thick, white or yellow exudate
    • Lips 🡪 ulceration with bloody crusting and painful

  • Microscopic description

    • Early lesions:

      apoptotic keratinocytes scattered in basal epidermis

    • Later lesions:

      numerous necrotic keratinocytes, full thickness epidermal necrosis and subepidermal bullae

  • HPA

    • Epidermal changes are often accompanied by a moderate or dense lymphocyte predominant dermal infiltrate
    • Less commonly, neutrophils and eosinophils are present
    • Less common findings are red blood cell extravasation, pigment incontinence, regenerating epidermis, parakeratosis

    

    

• TOXIC EPIDERMAL NECROLISYS

  • Called Lell’s disease

  • Secondary drug reaction

  • Increases apoptosis of the epithelial cell

  • Gambaran Klinis

    • SCALDED APPEARANCE: sloughing of skin an mucosa in large sheet
    • there are subepidermal bullae with widespread epidermal necrosis and subsequent separation or loss of the entire epidermis

  • Pathogenesis

    • Several immunopathologic pathways leading to keratinocyte apoptosis in TEN, including the following:
    • Fas ligand activation on keratinocyte membranes leading to death receptor–mediated apoptosis
    • Release of destructive proteins (perforin and granzyme B) from cytotoxic T lymphocytes (CTLs) generated from an interaction with cells expressing major histocompatability complex (MHC) class
    • Overproduction of T cell– and/or macrophage-derived cytokines (interferon-γ [INF-γ], tumor necrosis factor-α [TNF-α], and various interleukins)
    • Drug-induced secretion of granulysin from CTLs, natural killer cells, and natural killer T cells

    

  • HPA

    

    

• ORAL LICHEN PLANUS

  Oral lichen planus is a relatively common chronic inflammatory immunologic reaction in which epidermal or epithelial basal cell damage produces mucocutaneous lesions of various types

  • PATHOGENESIS

    It is a Tcell mediated autoimmune disease in which the cytotoxic CD8+ T cells trigger apoptosis of the basal cells of the raol epithelium. Several antigen specific and nonspecific inflammatory mechanism have been put forward to explain the accumulation and homing of CD8+ Tcells subepithelialially and the subsequent keratinocyte apoptosis

  • Clinically

    • asymptomatic
    • Usually present bilaterally
    • Most common site: posterior buccl mucosa
    • Other locations: tongue, gingiva,alveolar mucosa, palate, lip(mucosal side)
    • Characteristic feature: Wichams striae

  • Types of Oral Lichen Planus

    • Reticular form

      • Characterised by fine white lines or striae
      • striae may forma network or show annular patterns
      • Often displays a peripheral erythematous zone reflecting sub epithelial inflammation
      • buccal mucosa (bilaterally)

      

    • Papular

      • Usually present in intial phase of disease
      • Characterised :
        • small white dots
        • Minute white papules
        • These gradually enlarge to form either a reticular, annular, or plaque pattern
        • In most occasions it intermingles with Reticular form.

      

    • Plaque like

      • Shows a homogenous well demarcated white plaque oftenly but not always, surrounded by striae.
      • Most oftenly seen in smokers.
      • Confluent white patches similar to oral keratoses

      

    • Bullous

      • This form of OLP is quite rare.
      • May appear as Bullous structure surrounded by a reticular network.
      • The intraoral bullae rupture soon after they appear, resulting in the classic appearance of erosive OLP

      

    • Erythematous or Atrophic

      • Characterised by homogenous red area
      • In buccal mucosa or palate, striae are seen at periphery
      • May exclusively affect attached gingiva
      • presents as Desquamative Gingivitis
      • Can be very painfull
      • Red lesions often with a whitish border
      • May cause erosions.

      

    • Ulcerative

      Clinically, the fibrin - coated ulcers are surrounded by an eryhematous zone frequently displaying white striae.

      

  • HISTHOPATHOLOGY

    • Hyperorthokeratosis/Hyperparakeratosis
    • Acanthosis
    • Thickening of the granular cell layer
    • Basal cell liquefaction
    • Saw tooth configuration of the rete pegs
    • Band like dense inflammatory cellular infiltrate in the upper lamina propria

    

    

• ACTINIC KERATOSIS

  • DEFINITION
    • Also called solar keratosis, senile keratosis
    • Buildup of excessive keratin due to chronic exposure to sunlight
    • On sun-exposed sites (face, arms, dorsum of hands)
    • Called actinic cheilitis in lips
    • May become invasive with only a single layer of atypical keratinocytes

• Actinic Cheilitis

  • Actinic cheilitis, is a precancerous condition related to cumulative lifetime sun exposure.

  • The lower lip is most often affected

  • Individuals with actinic cheilitis often complain of persistent dryness and cracking of the lips. They will frequently exhibit other effects of sun-damaged skin, such as precancerous lesions on the skin called actinic keratoses and extensive wrinkling.

  • A certain type of skin cancer (squamous cell carcinoma) develops in 6–10% of cases of actinic cheilitis.

  • Signs and Symptoms

    Actinic cheilitis is located on the lips, most often the lower lip. Persistent redness, scaliness, and chapping are among the symptoms noted. Erosions and cracks (fissures) may be present as well.

    

  • HISTOPHATOLOGICAL

    • Basal cell and squamous layer atypia and disorderly maturation, hyperkeratosis, parakeratosis
    • May have atrophy of epidermal surface
    • Usually no granular layer except at follicular orifices
    • Elastosis and often chronic inflammation of dermis
    • Follicular apparatus and intraepidermal sweat duct are spared
    • May have coexisting melanocytic atypia

    

    

  • Differential diagnosis

    Superficially invasive squamous cell carcinoma

• Epitel displasia

  • kriteria

    • Architectutral features
      • irregular epithelial stratidication
      • loss of basal cell polarity
      • drop-shaped rete risges
      • increased number of mitotic figures
      • abnormally superficially mitoses
      • premature keratinixation in single cell (dyskeratosis)
      • kerain pearls with rete ridges
      • loss of epithelial cell cohesio\n
    • Cytologic features
      • abnormal variant in nuclear size (anisonucleosis)
      • abnormal variant in nuclear shape (nuclear pleomorphism)
      • abnormal variation in cell size (anisocystosis)
      • abnormal variation in cell shape (cellular pleomorphism)
      • increased nuclear/ cystoplasmic ratio
      • atypical mitotic figures
      • increased in number and size of nucleoli
      • hyperchromasia

  • morphological changes of anaplasia

    • pleomorphism

      variation in shape and size

    • abnormal nuclear morphology

      • hyperchromatic
      • large nucleus and irregular
      • nucleoli rpesent

    • mitosis

      • increase mitotic figure
      • atypical mitotic figure

    • loss of polarity

      disorganization of tumor cells

    • tumor giant cells

    

    

• Oral Mucosa Melanoma

  • Definition

    • malignant tumor originated from the proliferation of melanocytes cells that derived from the neural crest and that migrate to endodermal or ectodermal derived tissues, including mucosa
    • present at any location in the oral cavity, more frequently the hard palate and the maxillary alveolar mucosa

  • Clinical features

    • The color varies from brown to black pigmented with irregular border.

    • Early lesions

      flat macular extending lateral (radial growth phase)

    • Advanced lesions

      large, nodular, often with ulceration (vertical growth phase)

    • Positive cervical lymph nodes in 30% of cases at presentation

    

  • HPA

    

  • Microscopic Feature

    • pagetoid growth pattern (characterized by growth of melanoma cells in the upper layers of the epidermis)
    • The melanoma cells can be large and rich in cytoplasm, small or even spindly. In a subset of melanomas there are areas with abundant melanin and in other melanomas melanin pigment is scarce or absent.
    • Tumor cell nuclei are enlarged, often with a prominent nucleolus and mitoses are present at a variable degree

    

• POLYMORPHOUS LOW-GRADE ADENOCARCINOMA

  • Clinical features

    • arise from the minor salivary glands
    • a malignant epithelial tumor characterized by cytological uniformity, morphological diversity, an infiltrative growth pattern and low metastatic potential

  • Location

    hard and soft palate, upper lips and buccal mucosa

  • Sign and symptom

    asymptomatic swelling but occasionally can be painful and even ulcerate

    

  • MICROSCOPIC FEATURES

    • Non encapsulated but circumscribed tumor with polymorphous growth patterns (cribriform, solid, cords, cystic strand-like, tubular)
    • Infiltrative borders as small islands and tubules
    • Mucoid and hyaline stroma (may contain calcifications)
    • Tumor cells are round, polygonal shape with indistinct margin n pale eosinophilic cytoplasm

  • HPA

    A variety of architectural patterns can be appreciated in this low power view, including tubular (glandular), trabecular, solid, cribriform, single filing, and papillary. Architectural polymorphism is not unique to polymorphous low-grade adenocarcinoma and can be seen in many different salivary gland tumors. Note the residual benign minor salivary gland acini at the top.

    

    

    A variety of architectural patterns can be appreciated in this low power view, including tubular (glandular), trabecular, solid, cribriform, single filing, and papillary. Architectural polymorphism is not unique to polymorphous low-grade adenocarcinoma and can be seen in many different salivary gland tumors.

    

• ADENOID CYSTIC CARCINOMA

  • Formerly called cylindroma

  • Most common in mayor or minor salivary glands, involved the parotid, submaxillary and the accessory glands in palate and tongue

  • Slow-growing malignant but might be aggressive direct extension, perineural invasion and hematogenous metastasis

  • Symtoms

    local pain, facial nerve paralysis (parotid tumor)

  • Sign

    some lesion exhibit surface ulceration

    

  • MICROSCOPIC FEATURES

    • Cribriform pattern

      composed of small, deeply staining uniform cell, contain mucoid material producing 🡪 typical cribriform honey comb/ swiss cheese pattern

      

    • Tubular pattern

      the stromal connective tissue become hyalinized and sorrounds the tumor cell, forming the structural pattern tubular 🡪 derived cylindroma

      

• ORAL SQUAMOUS CELL CARCINOMA

  • a Malignant neoplasm of stratified squamous epithelium

  • capable of local destructive growth and distant metastasis

  • sites lower lip tongue floor of the mouth soft palate gingival / alveolar ridge buccal mucosa

  • The etiology is unknown, Association: Tobacco smoking and chewing, Chronic alcohol consumption, Human papilloma virus infection, carcinogen.

  • Appearance:

    • Ulceration with irregular shape and indurated margin
    • Broad base and dome like/ nodular
    • Red surface with white necrotic or keratin area

  • Sign n symptom:

    • Non healing ulcer, asymptomatic (exc infection)
    • Parasthesia
    • Lymph nodes : cervical node are commonly effected, enlarged and firm to
    • hard palpation

    

  • HPA

    • Increased mitotic activity
    • Keratinization varies
    • Hyperchromatic nuclei
    • Pleomorphism
    • Connective tissue stroma with chronic inflammation (histiocytes, lymphocytes, etc.)
    • Invasion and proliferation into connective tissue

    

    

    

    

    

  • DD

    • Well differentiated SSC
    • Moderately differentiated SSC
    • Poorly differentiated SSC

• BASAL CELL CARCINOMA

  • Arises from basal layer epidermis / hair follicle

  • Etiology

    ultraviolet radiation

  • Location

    exposed surface of skin, scalp, upper lips

  • Sign

    • small, slightly elevated papule which ulcerated 🡪 crusted ulcer
    • Lesion continuous to enlarge, infiltrate deeper tissue and may even into cartilage/ bone
    • Metastasize to lymph nodes

    

  • MICROSCOPIC FEATURES

    • Basaloid cells with scant cytoplasm and elongated hyperchromatic nuclei, peripheral palisading, peritumoral clefting and mucinous alteration of surrounding stroma
    • Types of BCC:
      • Adenoid BCC
      • Cystic BCC
      • Keratotic BCC
      • Solid/ primordial BCC 🡪 cell have little tendency to differentiate

  • HPA

    

    

• KAPOSI SARCOMA

  • derived from endothelial cell lineage.
  • Kaposi sarcoma can be primarily categorized into 4 types :
    • Epidemic (AIDS related)
    • Iatrogenic (immunosuppressant therapy related)
    • Classic, or sporadic
    • Endemic (African)

• CUTANEOUS LESIONS IN KAPOSI SARCOMA

  • Cutaneous lesions may occur at any location but typically are concentrated on the lower extremities and the head and neck region
  • Lesions may have macular, papular, nodular, or plaquelike appearances
  • Nearly all lesions are palpable and nonpruritic
  • Lesions may range in size from several millimeters to several centimeters in diameter
  • Lesions may assume a brown, pink, red, or violaceous color and may be difficult to distinguish in dark-skinned individuals
  • Lesions may be discrete or confluent and typically appear in a linear, symmetrical distribution, following Langer lines
  • Mucous membrane involvement is common (palate, gingiva, conjunctiva)
  • ORAL MANIFESTATION
    • Appear as a red, blue, or purplish lesion
    • Flat, solitary or multiple
    • Enlarge lesion may ulcerate and infection
    • Painful
  • HISTOPHATOLOGICAL

    • Consist band of spindle shape and or plump endothelial cell, atypical vascular channel, reticular or collagen fibers

    • Consist numerous capillary vessels with infiltration of inflammatory cell Late stage 🡪 nodule or lesion diffuse involvement of lamina propria

    • STAGE

      • Patch stage (macular) : proliferation of capillary vessel
      • Plaque stage : proliferation vascular channel with development of spindle cell
      • Nodular stage : spindle cell increase to form nodular tumor like mass

    • HPA