Skin pathology pigmented lesions neoplasms immune mediated lesions and infections
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Skin Pathology: Pigmented lesions, neoplasms, immune-mediated lesions, and infections. Lecture 5 Thursday, January 25, 2007 Refs. Basic Pathology Chapter 22 Wheater’s Basic Histopathology Chapter 21 Pathologic Basis of Disease 7th ed Chapter 25.

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Skin Pathology:Pigmented lesions, neoplasms, immune-mediated lesions, and infections

Lecture 5

Thursday, January 25, 2007

Refs. Basic Pathology Chapter 22

Wheater’s Basic Histopathology Chapter 21

Pathologic Basis of Disease 7th ed Chapter 25

Removing the Mystery of Eyelid Lesion Differential Diagnosis:Beyond Papilloma and Basal Cell Carcinoma

Thomas F. Freddo, O.D., Ph.D., F.A.A.O.

Professor of Ophthalmology, Pathology and Anatomy

Boston University School of Medicine


Adjunct Professor of Optometry

New England College of Optometry

Terms to describe skin lesions

  • Gross Lesions

    • Macule

    • Papule, nodule, plaque

    • Vesicle, bulla (blister)

    • Pustule

    • Wheal

    • Scale

    • Lichenification

    • Excoriation

Terms to describe skin lesions

  • Microscopic lesions

    • Hyperkeratosis, parakeratosis

    • Acanthosis,

    • Acantholysis, spongiosis

    • Lentiginous

    • Papillomatosis

  • Both gross and microscopic

    • Ulceration-complete loss of epidermis, ±defect in underlying dermis and subcutis

    • Erosion-incomplete loss of epidermis

Surface keratin wbp 21-1

Normal Hyperkeratosis Parakeratosis


Response of skin to disease

  • Limited repertoire

  • Few pathognomonic lesions

  • Acute dermatitis

    • Spongiosis

    • ± inflammatory infiltrate

    • If lesions are red, papulovesicular, oozing and crusted, the clinical term eczema can be used.

  • Chronic dermatitis

    • Acanthosis

    • Hyperkeratosis

Acute skin lesions Whp 21-5

Chronic skin lesions Whp 21-2

Pigmented lesions

  • Variation from benign to malignant

  • Benign conditions:

    • Vitiligo (loss of melanocytes and thus pigment from affected area) may be autoimmune, neurohumoral, toxic intermediates …..

    • Freckles (melanocyte number is normal but increased amount of melanin), melasma (hyperpigmentation on face)

    • Nevocellular nevus “mole”

      • Junctional, compound, intradermal

  • Dysplastic nevus may progress to malignant melanoma.

  • Malignant melanoma has tendency to metastasize.

Junctional nevus PBD 25-4

Compound nevus PBD 25-5, BP 22-19

Malignant melanoma BP 22-21A

Malignant melanoma BP 22-21C&DVertical growth (C) increases probability of metastasis.

Other skin tumors

  • Benign epithelial tumors-hundreds of kinds

    • Seborrheic keratoses, epithelial cysts, etc.

  • Actinic keratoses

    • Hyperkeratosis associated with chronic exposure to sunlight may become SCC.

  • Squamous cell carcinoma (SCC)

    • Sun exposure, rarely metastasizes, locally invasive

    • May present as non-healing ulcer.

  • Basal cell carcinoma

    • Slow growing, usually does not metastasize

    • Sun exposure is a predisposing factor.

Papillomatous Masses:Seborrheic keratosis






with greasy


Seborrheic keratosis PBD 25-9 (BP 22-13)

Actinic Keratosis

Actinic keratosis - can also appear as a scaly papule. Again note blotchy appearance of surrounding skin.

Actinic keratosis - the scaly appearance is actually parakeratosis indicating rapid turnover of the epithelium. The basal half of the epithelium looks worrisome, with lateral budding of the rete pegs, but the apical half looks OK. Squamous cell CA-Grade 1/2.

Rounded, symmetric dome with central nidus of keratin vs non-domed irregular border with larger central crater of keratin

Squamous cell



The other major clue to this differential is how long the lesion has been present.

Squamous cell carcinoma BP 22-17b&c

Basal Cell Carcinoma

  • Commonest form of skin cancer

  • Typically seen on sun-exposed areas such as the face and neck.

  • Originate from the basal keratinocyte

  • Histologically reminiscent of skin adnexal structures such as hair follicles.

  • Locally invasive, but rarely metastasize

Basal Cell Carcinoma

  • Age of onset: >40 years of age.

  • Sex: Males > females.

  • Incidence: In US, 500-1,000 per 100,000; >400,00 new cases each year.

  • Race: Higher in Caucasians, rare in brown and black skinned people.

  • Predisposing factors:  White-skin with poor tanning capacity, albinos, exposure to x-rays for facial acne, arsenic ingestion, heavy sun exposure before age 14.

Basal Cell Carcinoma - Types

  • 1) Nodular (and nodulo-ulcerative): Most common.  Begins as a small, skin-colored papule which shows fine telangiectasia and a glistening pearly edge.  Frequently, there is central necrosis that leaves a small ulcer with an adherent crust.  They are usually less than 1 cm in diameter (I.e. NODULES), but grow larger if present for several years.

NodularBasal Cell CA

Basal Cell Carcinoma

Nodulo-ulcerative type

Nodulo-ulcerative Basal Cell CA



vessels near



Differential Diagnosis:Nodulo-ulcerative Basal Cell CA vs Squamous cell carcinoma

Squamous cell - Central crater dry, filled with brown-yellow, scaly, greasy keratin

Basal Cell - Central crater ulcerated and moist, often with hemorrhage and translucent border

Cystic Basal Cell Carcinoma

  • Cystic: Become tense and translucent, and show cystic spaces on histology

Basal cell carcinoma BP 22-18b,c


  • Infectious

    • Secondary to systemic disease

    • Primary infections

      • Bacterial - impetigo usually Staph or Strep

      • Viral- warts due to human papillomavirus

        • Molluscum contagiosum caused by pox virus

      • Fungal due to dermatophytes-tinea capitis, barbae, pedis, corporis

Erythema multiforme BP 22-3a hypersensitivity to infections and drugs

Psoriasis BP 22-4 and 22-5Current evidence: mediated by T cells

Papillomatous Masses:Verruca vulgaris

  • Scaly

    nodule with



    Sometimes in


    At lid margin, can give rise to follicular conjunctivitis, like mollsucum.

Wart (Verruca vulgaris) Whp 21-9

Acne vulgaris

  • Physiological hormonal variations and alterations in hair follicle maturation

    • Androgens

    • Dilation of follicle with sebum and keratin

  • Comedones

    • Open- has black keratin plug

    • Closed- can rupture- severe inflammation

Acne (hair shaft piercing follicular epithelium associated with inflammation) PBD 25-42

Blistering diseases

  • Group of diseases with vesicles and/or bullae as major features

  • Location of vesicles varies (see fig. 22-7)

  • Subcorneal vesicles are more superficial

    • Pemphigus foliaceus

  • Suprabasal vesicles are above the stratum basale.

    • Pemphigus vulgaris

  • Subepithelial vesicles are at junction of basal cells and basement membrane.

    • Bullous pemphigoid and dermatitis herpetiformis

Pemphigus vulgaris BP 22-8 B

Pemphigus vulgaris. Direct immunofluorescence shows antibody and complement at intercellular junctions of keratinocytes. BP 22-9

Bullous Pemphigoid BP 22-10

Bullous Pemphigoid BP 22-11A

Dermatitis herpetiformis. IgA is deposited at the tips of dermal papillae BP 22-12

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