Introduction to Disorders of the Skin

Question 1

What are the non-neoplastic skin disorders?

Answer 1

1) Freckle (Ephelis): very common, due to degree of pigmentation, cyclical variation (sun exposure) in pigment intensity
2) Lentigo: benign localized hyperplasia of melanocytes in linear fashion along basement membrane

Question 2

Describe a Melanocytic Nevus

Answer 2

• uniformly pigmented, usually <6mm in diameter
• well circumscribed borders
• hormone sensitivity –> variable prominence; no change in size
• 3 types: junctional (D-E junction); compound (vertical growth into dermis); intradermal

Question 3

Describe Neoplastic-Dysplastic Nevi

Answer 3

• some progress to malignant melanoma (most do not)
• most >5mm in diameter
• flat (macules); raised plaques with “pebbly” surface; target-like lesions with raised center and feathery periphery
• variegation (variable pigmentation)
• not restricted to sun exposed areas

Question 4

Describe Neoplastic-Malignant Melanoma

Answer 4

• most deadly of all skin cancers
• relatively common neoplasm
• can be cured if detected and treated early
• located on skin, mucosa, meninges, uvea of eye
• most cases are sporadic
• asymmetry; irregular borders; variations in color; diameter increase
• radial growth phase and vertical growth phase

Question 5

What are the genetic features of a nevi?

Answer 5

• benign neoplasm

- constitutive activations in RAS or the serine/threonine kinase BRAF

Question 6

What are the genetic features of a dysplastic nevi?

Answer 6

• can be direct precursor of melanoma, but most are not

- RAS and BRAF activating mutations + loss of function of CNDK2A mutations

Question 7

What are the genetic features of melanoma?

Answer 7

driver mutations:

• CDKN2A: disrupt cell cycle control
• RAS: activate growth promotion
• TERT: telomerase activation

Question 8

What is Seborrhic keratoses?

Answer 8

• benign tumor
• very common for middle-aged+
• trunk…+extremities head and neck
• round, flat, “coin like”, waxy –> “like a sticker”
• can be part of paraneoplastic syndrome; GI cancers

Question 9

What is Fibroepithelial polyp?

Answer 9

• benign tumor
• very common cutaneous lesion
• middle-aged+
• neck, trunk, face, intertriginous areas
• ex. skin tag; acrochordon, squamous papilloma

Question 10

What is actinic keratoses?

Answer 10

• premalignant tumor
• sun-damaged skin
• hyperkeratosis
• progressively worsening dysplastic change –> can progress to SCC
• rough, sand-papery feel

Question 11

What is SCC?

Answer 11

• malignant tumor
• 2nd most common tumor arising in sun-exposed sites in adults
• prominent role of UV radiation
• oncogenic viruses: HPV subtypes 5 and 8

Question 12

What is BCC?

Answer 12

• malignant tumor
• most common invasive cancer in humans worldwide; most common skin cancer
• slow-growing; rarely metastasized
• sun-exposed sites
• pearly papules with prominent dilated blood vessels (telangiectasias)

Question 13

What is pemphigus vulgaris?

Answer 13

• superficial vesicles and bullae
• rupture easily leaving shallow erosions and crust
• IgG autoantibodies directed againts components of desmosomes
• net-like direct immunoluorescence staining pattern in epidermis highlights intracellular IgG deposition
• produces ancantholysis: lysis of intracellular bridges produce suprabasal blisters

Question 14

What is bullous pemphigoid?

Answer 14

• elderly individuals
• autoantibodiess directed against components of hemidesmosomes
• sub-epidermal, non-acantholytic blisters