15.6 Integumentary System Pathology: Inflammatory Dermatoses, Blistering Disorders, and Skin Neoplasms
Key Takeaways
- Pemphigus vulgaris is an intraepidermal (suprabasal) blistering disease with anti-desmoglein-3 antibodies, positive Nikolsky sign, and oral mucosal involvement, whereas bullous pemphigoid is a subepidermal disease of the elderly with tense blisters and a negative Nikolsky sign.
- Basal cell carcinoma is the most common skin cancer, arising in sun-exposed areas with a pearly papule and rolled telangiectatic border; it rarely metastasizes, unlike squamous cell carcinoma which can spread to lymph nodes.
- Melanoma prognosis is determined by Breslow depth, and superficial spreading is the most common subtype; BRAF V600E mutations are present in roughly half of cutaneous melanomas and guide targeted therapy.
- Psoriasis shows thick silvery scale over extensor surfaces with nail pitting and is characterized histologically by parakeratosis with Munro microabscesses and the Koebner phenomenon at sites of trauma.
- Erythema multiforme produces target lesions often triggered by HSV or mycoplasma; its severe forms are Stevens-Johnson syndrome and toxic epidermal necrolysis.
15.6 Integumentary System Pathology
Skin pathology on NPLEX is vignette-driven: a description of the lesion's appearance, distribution, and association is usually enough to reach the diagnosis. The blueprint lists eight disease categories; this section moves through each, pairing morphology with mechanism.
1. Pigmentation and Genetic Disorders
Nevocellular nevi are benign melanocytic proliferations. Vitiligo is autoimmune destruction of melanocytes producing well-demarcated depigmented macules. Albinism is absent melanin from a tyrosinase defect (oculocutaneous), with photophobia and nystagmus from foveal hypoplasia. Ehlers-Danlos syndrome (collagen defect) produces hyperextensible skin and joints and vascular fragility in the vascular subtype (type III collagen or vascular EDS).
2. Acute and Chronic Inflammatory Dermatoses
Atopic dermatitis (eczema) is a type I hypersensitivity with elevated IgE, pruritus, and lichenification from chronic scratching, beginning in childhood in flexural areas (antecubital and popliteal fossae). Contact dermatitis is a type IV delayed reaction (e.g., poison ivy, nickel), spongiotic on histology, restricted to the area of contact. Urticaria is transient wheals from mast-cell mediator release. Erythema multiforme produces target lesions triggered by HSV, mycoplasma, or drugs; severe mucosal involvement defines Stevens-Johnson syndrome and extensive epidermal detachment (>30% body surface) defines toxic epidermal necrolysis, usually drug-induced.
Psoriasis is a chronic TH17-mediated hyperproliferative disorder. It favors extensor surfaces (knees, elbows, scalp), shows thick silvery scale, nail pitting, and an associated arthritis; Auspitz sign (bleeding when scale removed) and Koebner phenomenon (lesions at trauma sites) are classic. Histology: parakeratosis, Munro microabscesses (neutrophils in the stratum corneum), loss of the granular layer, and regular acanthotic epidermal elongation. Lichen planus is the 'six Ps'—purple, pruritic, polygonal, planar papules and plaques on the wrists and ankles, with oral Wickham striae. Acne rosacea is central-facial erythema with papulopustules, telangiectasia, and late rhinophyma; acne vulgaris is Cutibacterium acnes-driven androgen-mediated follicular inflammation with open and closed comedones, treated with retinoids, benzoyl peroxide, and for severe nodulocystic disease, oral isotretinoin.
3. Blistering Diseases
| Disease | Blister level | Antibody | Clinical |
|---|---|---|---|
| Pemphigus vulgaris | Intraepidermal, suprabasal | Anti-desmoglein-3 | Flaccid blisters, Nikolsky +, oral mucosa |
| Bullous pemphigoid | Subepidermal | Anti-BP180/BP230 (hemidesmosome) | Tense blisters, elderly, Nikolsky − |
| Dermatitis herpetiformis | Subepidermal | Anti-endomysial / tTG | Pruritic elbows/knees, celiac disease |
| Epidermolysis bullosa | Varies (genetic) | Structural (e.g., keratin) | Blistering from minor trauma, congenital |
Pemphigus vulgaris is severe and mucosal; bullous pemphigoid is milder and lacks mucosal involvement. Dermatitis herpetiformis, with its granular IgA at dermal papillae, responds to a gluten-free diet and dapsone.
4. Benign, Pre-malignant, and Malignant Lesions
Seborrheic keratosis is a benign 'stuck-on' waxy plaque of the elderly (the sudden eruptive form is Leser-Trélat sign, a marker of internal malignancy). Actinic keratosis is a premalignant rough scaly sun-damage lesion that can progress to squamous cell carcinoma. Dysplastic nevi are atypical moles; in familial atypical multiple mole melanoma (FAMMM) syndrome they confer high melanoma risk.
Basal cell carcinoma (BCC) is the most common skin cancer, on sun-exposed skin, a pearly papule with rolled border and telangiectasias, from PTCH/p53 pathway mutation; locally invasive but rarely metastasizes. Squamous cell carcinoma (SCC) arises in sun-damaged skin or scars, produces keratin pearls, and can metastasize to regional lymph nodes. Melanoma: ABCD (Asymmetry, Border irregularity, Color variation, Diameter >6 mm) with evolution; Breslow depth is the strongest prognostic factor. Subtypes: superficial spreading (most common), nodular (worst prognosis, vertical growth), lentigo maligna melanoma (sun-damaged elderly), acral lentiginous (palms, soles, subungual; not sun-related, more common in darker skin). About half carry BRAF V600E, targeted by vemurafenib and dabrafenib.
5. Infectious Dermatological Diseases
Impetigo is a superficial Strep/Staph infection with honey-colored crust; the bullous form is Staph exfoliatin. Cellulitis is spreading Strep pyogenes/Staph aureus dermal infection (warm, erythematous, poorly demarcated); erysipelas is a more superficial Strep form with sharp, raised borders, classically affecting the face. Erythema nodosum is painful shin nodules, a delayed hypersensitivity to Strep, sarcoidosis, IBD, or drugs. Folliculitis is Staph hair-follicle infection; furuncle and carbuncle are deeper. MRSA is methicillin-resistant Staph aureus. Molluscum contagiosum is a poxvirus with umbilicated papules and cytoplasmic Henderson-Paterson bodies. Verrucae (warts) are HPV-driven. Tinea is dermatophyte (Trichophyton) infection: capitis (scalp), corporis (body), cruris (groin 'jock itch'), pedis (athlete's foot). Candidiasis is Candida, often intertriginous; oral thrush in immunocompromised patients. Acne vulgaris is included among infections because C. acnes drives follicular inflammation.
Board signal: an elderly patient with tense bullae and negative Nikolsky → bullous pemphigoid; a sun-exposed pearly papule that bleeds → basal cell carcinoma; a pigmented lesion with irregular borders and recent change → melanoma with Breslow depth guiding prognosis.
A 70-year-old man presents with multiple tense fluid-filled bullae on the trunk and arms but no oral involvement. Nikolsky sign is negative. Biopsy shows a subepidermal blister. Which antibody target confirms the diagnosis?
A 54-year-old fair-skinned sailor has a 1.2 cm irregularly pigmented lesion on his back with notched borders and recent color change. Excision shows melanoma. Which histologic feature most strongly predicts prognosis?