Integumentary Pathology

Terminology

• Plaque

• Scale

• Onycholysis

• Vesicle

• Bulla

• Acanthosis

• Hyperkeratosis

• Parakeratosis

• Acantholysis

• Erosion

• Ulceration

• Plaque: raised flat-topped lesion, usually >5mm diameter

• Scale: dry flakes that can easily be scraped away due to thickened corneal layer

• Onycholysis: separation of nail plate from nail bed

• Vesicle: small fluid-filled blister usually <5mm diameter

• Bulla: larger fluid-filled blister, usually >5mm diameter

• Acanthosis: epidermal thickening due to hyperplasia, stratum spinosum increases

• Hyperkeratosis: Increase in thickness of stratum corneum

• Parakeratosis: Retention of nuclei in stratum corneum

• Acantholysis: loss of intercellular cohesion between keratinocytes

• Erosion: Incomplete loss of epidermis

• Ulceration: complete loss of epidermis revealing dermis or hypodermis

Psoriasis

• Define

• Pathogenesis

• Macroscopic Morphology aka Clinical Presentation

• Microscopic Morphology

• Chronic proliferative, non-infectious inflammatory disease

• Pathogenesis: arises due to both genetic factor as well as immunological factors (Th1 and Th17 mediated) and environmental factors (local trauma/Koebner phenomenon)

• Macroscopic Morphology: well demarcated pink to salmon-colored plaques covered with silvery-white scales

  • Removal of scales causes petechial bleeding (Auspitz sign)

  • Onycholysis and oil spots in nails

  • Skin, elbows, knees

  • Palliative treatment only

    

• Microscopic Morphology:

  • Acanthosis with downward elongation of rete ridges

  • Extensive parakeratosis scaling

Pemphigus Vulgaris and Foliaceous

• Define

• Pathogenesis

• Micro Morphological features

• Macro-Morphological features/Clinical Features

• Autoimmune blistering disorder caused by the separation of two layers within the epidermis

  • Vulgaris: suprabasal separation

  • Foliaceous: subcorneal separation

    

• Pathogenesis: causes by antibody-mediated type II hypersensitivity, which causes degradation of desmosomes by plasmin

  • Vulgaris: antibodies against desmoglein (DSG) 1 and 3

  • Foliaceous: antibodies against DSG1 only

    

• Micro Morphological features:

  • Vulgaris: Acantholysis leads to tombstone cells in stratum basale

    • Fishnet pattern caused by IgG deposition upon fluorescence

      

  • Foliaceus: acantholysis in stratum granulosum, IgG deposits only on superficial layers

    

• Macro-Morphological features/Clinical Features

  • Vulgaris: blisters that easily coalesce forming bullae and rupture leaving superficial erosions covered with serum crust; new lesions occurs by gently rubbing (Nikolsky sign+)

    • Begin as painful blisters in oral mucosa then spread

  • Foliaceus: more superficial with smaller zones of erythema and crusting

    • never in oral mucosa

      

Bullous Pemphigoid

• Define

• Pathogenesis

• Clinical Features

• Chronic bullous disorder with an autoimmune basis affecting 60-80 yo

  • Less severe and more common than pemphigus vulgaris

• Pathogenesis: IgG auto-antibodies against basement membrane proteins BPAG1 and BPAG2 through mast cell degranulation

• Clinical Features

  • Subepidermal bullae

  • Unlikely oral involvement 10%

  • Multiple tense 2cm bullae on erythematous base, do not rupture easily

  • No acantholysis

  • Heals w/o scarring

    

Melanocytic Nevus

• Define

• Micro-Morphology

• Benign proliferation of nevus cells, a mole

  • Linked to sun exposure and innate susceptibility

• Micro-Morphology: Nests of uniform round cells with inconspicuous nucleoli and few mitotic figures

Dysplastic Nevus

• Define

• Micro-Morphology

• Lesions with variable pigmentation and irregular borders, usually larger than normal nevi

  • Increases risk for melanoma

• Micro-Morphology: irregular nests that bridge

Melanoma

• Define

• Linked to

• Pathogenesis

• Morphology

• Types of spread

• Tumor markers

• Malignant neoplasm of melanocytes

• Strongly linked to mutations caused by exposure to UV radiation

  • Leading cause of mortality in young adults

• Pathogenesis: caused by UV radiation damaging DNA of melanocytes; hereditary predisposition 5-10%

  • Mutations in CDKN2A gene disrupt cell cycle oncogenes

  • Mutations in BRAF and NRAS genes activate MAPK pathway

• Morphology: variation in pigmentation, larger size >mm, Irregular notched borders

• Types of spread:

  • Superficial

  • Lentigo: radial growth on face

  • Nodular: vertical growth and rapidly growing

  • Acral lentiginous: palms soles and nail beds get coloration in dark individuals; not related to UV exposure

• Tumor markers: S-100 and HMB-45 and use ABCDE guide

Actinic Keratosis

• Define

• Pathogenesis

• Micro Morphology

• Pre-cancerous lesions tht may progress to squamous cell carcinoma

  • circumscribed tan-brown or red lesions <1cm in diameter that are sand-paper like

• Pathogenesis: caused by UV-induced DN damage associated with TP53 mutations

• Micro Morphology: basal keratinocytes show dysplasia

  • Parakeratotic scales and elastosis

Basal Cell Carcinoma

• Define

• Pathogenesis

• Morphology (macro and micro)

• Most common form of skin cancer, may be locally aggressive but metastases is rare

• Pathogenesis: caused by mutations (due to UV) in the PTCH1 gene or TP53 for both sporadic and familial

• Morphology:

  • Pearly papule lesion that may be 2-3mm

  • telangiectasia

    

  • Nests of deeply basophilic epithelial cells, and separation clefts

    

Squamous Cell Carcinoma

• Define

• Pathogenesis

• Morphology (micro and macro)

• 2nd most common type of skin cancer that typically occurs in sun exposed areas

• Pathogenesis: most are mutated TP53 genes

• Morphology: red scaling plaques that may ulcerate in ears hands lips and hands

  • Entire epidermis is replaced by dysplastic keratinocyte

  • Only metastasize after long periods of time