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L 20 Dermatology Study Notes: Benign and Malignant Pigmented Skin Lesions and Other Skin Conditions

Fitzpatrick Classification

  • Developed in 1975 by dermatologist Thomas B Fitzpatrick to estimate melanogenesis of different skin types in response to UV light; used historically to guide phototherapy and phototoxic risk assessment.
  • Purpose: estimate how skin responds to ultraviolet exposure and photochemotherapy (e.g., PUVA) across skin phototypes.
  • Classification framework referenced: Table 3 (Skin type and tanning ability) based on Fitzpatrick skin pigmentation scale.
  • Key takeaway: skin type affects risk of phototoxic reactions and melanoma risk profile; exact type labels (I–VI) correspond to increasing ability to tan and decreasing burn risk, with type I being very light/pale and type VI being very dark.

Skin Neoplasms Line-up (benign vs malignant)

  • Benign neoplasms included in the lineup:
    • Seborrheic keratosis (SK)
    • Acrochordons (skin tags)
    • Hemangiomas
    • Lentigines
    • Nevi (melanocytic nevi, moles)
    • Lipoma
  • Malignant neoplasms included:
    • Actinic keratosis (AK)
    • Keratoacanthoma
    • Basal cell carcinoma (BCC)
    • Squamous cell carcinoma (SCC)
    • Malignant melanoma
  • Overall aim: describe general features, presentation, exam findings, imaging/biopsy considerations, and treatment approaches for each lesion type.

Distinguishing Features: Benign vs Malignant (general clues)

  • Benign characteristics:
    • Small size typically < 5–6 mm
    • Slow growth
    • Distinct, well-defined borders
    • Symmetrical shape
    • Regular pigment distribution
  • Malignant characteristics:
    • Larger size often > 6 mm
    • Rapid growth tendency
    • Indistinct or irregular borders
    • Asymmetry
    • Irregular pigment or color variation
  • Use of these features helps triage which lesions warrant biopsy or excision for histopathologic confirmation.

Tissue Analysis and Biopsy: purposes and types

  • Why biopsy/ tissue analysis:
    • Uncertainty of diagnosis
    • Poor response to treatment
    • Evaluate evolution of a condition into another
    • Investigate symptoms without familiar disease
  • Biopsy types:
    • Superficial shave biopsy
    • Deep shave biopsy
    • Curettage
    • Punch biopsy
    • Incisional/excisional biopsy
  • Superficial shave biopsy:
    • For epidermal lesions; does not assess dermis well
    • Technique: scalpel (#15 or #11 blade) shave the superficial lesion
  • Deep shave biopsy:
    • For non-melanoma skin cancers; tangential shave to mid-dermal level
  • Curettage:
    • Removes superficial lesions confined to epidermis; leaves fragments; not ideal when histology is needed
  • Punch biopsy:
    • Circular core; diameter 0.5–8.0 mm
    • Defect is circular and may require suture
    • Should not be used for melanocytic lesions
  • Incisional/excisional biopsy:
    • Removal of portion (incisional) or entire lesion (excisional) using scalpel
  • Mohs Micrographic Surgery:
    • Specialized removal of dermatologic cancers with pathology; goal: remove cancer while sparing maximum healthy tissue
    • 100% microscopic margin examination
    • Highest evidence-based cure rates for cutaneous malignancies (BCC/SCC, etc.)
    • Important in cosmetically/functionally sensitive areas (periorbital, nasal, auricular, perioral, digital, anogenital)
  • Mohs indications (when to consider):
    • Recurrent tumors
    • High-risk anatomic locations (central face, eyelids, eyebrows, nose, lips, chin, ear, anogenital region, hands, feet, nails, ankles, nipple/areola)
    • Aggressive histologic subtype
    • Perineural invasion
    • Tumor size > 2 cm
    • Poorly defined clinical borders
    • Rapid growth
    • Positive margins on recent excision

Seborrheic Keratosis (SK)

  • Epidemiology:
    • Most common benign cutaneous neoplasm
    • Genetic predisposition: autosomal dominant inheritance with incomplete penetrance
    • Typically appears during the 4th decade of life
  • Pathophysiology:
    • Benign proliferation of immature keratinocytes
  • Description on exam:
    • Brownish, mulberry-shaped, verrucous (wart-like)
    • 3–20 mm diameter macules, papules, or plaques with overlying scale
    • “Stuck-on” or pasted appearance; waxy surface; horn cysts
    • Usually asymptomatic or mildly pruritic; irritated SKs may be tender or crusted
    • Carcinomatous processes (SCC, BCC, melanoma, keratoacanthoma) have been reported within/adjacent to SK
  • Location:
    • Trunk and face; not on mucous membranes, palms, or soles
  • Leser-Trélat sign:
    • Rare cutaneous marker of internal malignancy (gastric, colonic, breast, lymphoma) with sudden increase in number/size of SKs, skin tags, and acanthosis nigricans
  • Treatment:
    • None required; cosmetic or functional impairment warrants intervention
    • Options: cryosurgery, curettage, shave excision, electrodessication, laser (erbium:YAG)
    • Biopsy may be required if appearance is inflammatory or pigmented dark lesions

Acrochordon (Skin Tags)

  • Epidemiology:
    • Increase with age, obesity, diabetes, pregnancy, friction
  • Description:
    • Soft, fleshy, tan to brown pedunculated polyps
    • Size: 1 mm – 2 cm
    • Common locations: neck (35%), chest, axilla (48%), inner thighs (intertriginous areas)
  • Treatment:
    • None required
    • Simple tangential excision; aluminum chloride can be used for hemostasis; electrodessication

Hemangiomas

  • Types:
    • Cherry hemangiomas (adult onset; most common acquired benign vascular proliferation)
    • Infantile hemangiomas (most common benign tumors of infancy; grow rapidly in first weeks of life)
  • Epidemiology:
    • Infantile: female > male; associated with low birthweight, white ethnicity, preterm birth, older maternal age, placenta previa, preeclampsia
    • Adult/other: estrogen exposure and certain medications; strongest risk factor for cherry angiomas is age
  • Pathophysiology:
    • Infantile: vascular anomaly of placental/fetal origin
    • Cherry angioma: benign vascular proliferation
  • Description:
    • Common soft tissue tumors of proliferating vessels, often on head/neck
    • Infantile: “strawberry” or cavernous types
    • Adult: cherry-type lesions
    • Erythematous or purple nodules/papules
  • Investigations:
    • Infantile lesions: ultrasound can be used; biopsy rarely indicated
    • Large lesions (>5 cm) like lumbosacral involvement: imaging of abdomen/pelvis; liver ultrasound if >5 lesions in infant
  • Treatment:
    • Cherry angioma: usually none
    • Infantile hemangioma: many involute spontaneously by age 10; ophthalmology referral for periorbital lesions; propranolol is the gold-standard for severe cases; laser therapy as needed

Lentigines (Simple/Solar)

  • Epidemiology:
    • Associated with advancing age (30–40s); present in ~90% of Caucasians >60 y/o; sun-exposed areas; independent melanoma risk factor
  • Pathophysiology:
    • Increased activity of epidermal melanocytes; do not fade with cessation of sun exposure
  • Description:
    • Circumscribed tan to brown to black macules; round-to-oval; typically < 5 mm in simple lentigines
    • Flat (non-palpable)
  • Types:
    • Simple lentigines (solar) vs. other lentiginous lesions
  • Treatment:
    • Cosmetic options: cryosurgery, laser, chemical peels, bleaching creams
    • Excision if suspicious for malignancy

Melanocytic Nevi (moles)

  • Definitions:
    • Three dermatologic definitions: (1) congenital birthmark, (2) benign tumor of melanocytes, (3) hamartoma (benign malformation with excess/deficient structural elements)
  • Epidemiology:
    • Appear in childhood and adulthood
    • Common range: about 10–40 nevi; having >50 nevi increases melanoma risk with sun exposure/heredity factors
  • Pathophysiology:
    • Benign proliferation of melanocytes (nevus cells)
    • Types: junctional, dermal, compound
  • Histopathology (clinical/histologic features):
    • Junctional: dark brown macule with lighter brown rim; nests of small, uniform nevomelanocytes at the dermal–epidermal junction
    • Compound: light to medium brown papule with junctional and dermal nests of nevus cells
    • Intradermal: soft pink papule with nests of nevus cells within the dermis
  • Description (clinical):
    • Small (<1 cm) circumscribed pigmented macules/papules
    • Well-demarcated, symmetric, uniform in contour and color (tan to brown)
    • Blue nevi: 0.5–1 cm, rounded, well-defined
  • Management:
    • Longitudinal observation; excision if suspicious/atypical/changes/repeated trauma or cosmetic concerns
  • Atypical nevi:
    • Noted as distinct in presentation; image references provided in source materials

Lipoma

  • Epidemiology:
    • Genetic predisposition; more common in adults >30 y/o
    • Increased incidence in overweight individuals, diabetes, and elevated serum cholesterol
  • Pathophysiology:
    • Mature adipocytes enclosed by a thin fibrous capsule
  • Description:
    • Single or multiple
    • Soft, rounded, lobulated, movable with normal overlying skin
    • Typically a few cm; can enlarge to > 6 cm
    • Nontender
    • Common locations: neck, trunk, extremities
  • Treatment:
    • None or surgical excision if symptomatic or cosmetically bothersome

Actinic Keratosis (AK)

  • Epidemiology:
    • Sun-exposed areas, fair skin (Fitzpatrick I–II), elderly, photodamage
    • Considered precancerous with atypical epidermal cells confined to the epidermis
    • Marker for increased risk of SCC, BCC, andMM; one of the most frequently encountered skin lesions in derm practice
  • Pathophysiology:
    • Proliferation of atypical epidermal keratinocytes
    • Progression risk to low-grade SCC ranges from 0.025% to 15%
  • Description:
    • Single or multiple lesions
    • Rough, erythematous plaques/papules; may be pigmented
    • Keratotic scale, crusted or ulcerated
    • Better felt than seen; adjacent sun-damaged skin shows signs of damage (yellow/pale coloration, spotty hyperpigmentation, telangiectasias, xerosis)
  • Treatment:
    • Surgical excision/biopsy if needed
    • Cryotherapy
    • Topical 5-FU
    • Chemical peels
    • Topical imiquimod or retinoids

Basal Cell Carcinoma (BCC)

  • Epidemiology:
    • Most common skin cancer
    • Fair-skinned individuals (Fitzpatrick I–II); incidence increases with age
    • Sun exposure and genetics contribute; immunosuppression is a risk factor
    • Metastasis is rare and almost never fatal
  • Pathology:
    • Arises from basal layer of epidermis and its appendages
  • Presentation/Description:
    • Often presents as a papule/nodule with translucent/pearly rolled border and a depressed ulcer or scab; telangiectasias commonly seen
    • 85% occur on the head and neck; 25–30% occur on the nose
  • Diagnosis:
    • Biopsy: punch, shave, or excisional
  • Treatment:
    • Surgical modalities: standard excision with 4–5 mm margins; electrodessication and curettage (ED&C); Mohs surgery (highest cure rates)
    • Topical therapies for select cases: imiquimod (daily Mon-Fri for 6 weeks; trunk/neck/extremities only; higher recurrence in 3 years), 5-fluorouracil (5-FU) topical therapy
    • Prevention: total body skin exams at least annually

Squamous Cell Carcinoma (SCC)

  • Epidemiology:
    • Associated with advancing age and light skin phototype (Fitzpatrick I–II), freckles, red hair
    • Sun exposure and carcinogens (smoking) contribute; immunosuppression and HPV-related SCC (particularly head/neck)
    • Skin cancers in people of color have different presentations; 2–5% metastasize
  • Pathology:
    • Dysplastic keratinocytes with malignant behavior
  • Description/Clinical features:
    • Slowly evolving, isolated keratotic or eroded papule/plaque
    • Common sites: scalp, backs of hands, pinna
    • SCC in situ (Bowen’s disease) is a common presentation: erythematous scaling patch or slightly elevated plaque
    • In skin of color, presentations are broader with ill-defined pink patches or hyperkeratotic plaques
  • “Clinical pearl”: any isolated keratotic or eroded lesion persisting >1 month should be treated as carcinoma until proven otherwise
  • Treatment:
    • Mohs surgery for high-risk tumors or cosmetically sensitive areas; higher cure rates
    • Standard excision with 4–6 mm clinical margins to a depth of the mid-subcutaneous fat for low-risk tumors
    • Electrodessication and curettage (ED&C)
    • Topical or intralesional chemotherapy
    • Local radiation when surgery contraindicated or for palliation
    • Prevention: total body skin exams at least annually

Malignant Melanoma

  • Epidemiology:
    • Most deadly form of skin cancer; responsible for >90% of skin cancer deaths
    • Approximately 8,430 deaths per year; incidence rising by roughly 3–7% annually
    • Lifetime risk estimates: about 1 in 48–51 individuals
    • Precursor lesions include congenital nevi, dysplastic nevi, and lentigo maligna
    • Genetic risk factors and sun exposure (tanning behaviors) strongly influence risk; phototypes I & II (red hair) at higher risk; history of many nevi or lentigines raises risk
  • Pathology and prognosis:
    • Proliferation of malignant melanocytes
    • Breslow depth (tumor thickness) is the most important prognostic factor; thickness is measured as depth into the skin (historically in millimeters, often reported in μm for precision)
    • Breslow depth is used to guide surgical margins and adjuvant therapy decisions
  • Description and subtypes (clinical/histopathologic):
    • Four main primary cutaneous melanoma subtypes:
    • Superficial spreading melanoma (SSM) – ~57.4%, median age ~51
    • Nodular melanoma (NM) – ~21.4%, median age ~56
    • Lentigo maligna melanoma (LMM) – ~8.8%, median age ~68
    • Acral lentiginous melanoma (ALM) – ~4%, median age ~63; more common in skin of color
    • Unclassifiable melanoma (UCM) – ~3.5%
    • Others ~5%
    • Key clinical rule: A-B-C-D-E-F (see below) and Ugly Duckling sign
  • A-B-C-D-E-F (Melanoma assessment framework):
    • A = Asymmetry of the lesion
    • B = Borders irregular
    • C = Colors multiple
    • D = Diameter > 6 mm
    • E = Evolution (change over time)
    • F = Funny looking (Ugly duckling sign)
  • Common site distribution:
    • Often posterior trunk in men; legs in women
  • Staging and prognosis:
    • TNM staging (AJCC system; updated 2000, 2009, 2017)
    • Factors: tumor thickness, ulceration, nodal involvement, distant metastasis
    • Prognosis depends on stage at diagnosis; total body skin exam (TBSE) essential
  • Diagnostic and treatment workflow:
    • Referral to melanoma specialist
    • Re-excision with margins based on Breslow depth; Mohs if very small or facial lesions
    • Lymph node evaluation: ultrasound, biopsy, sentinel lymph node biopsy (SLN), or lymph node dissection as indicated
    • Imaging (CT, CXR, PET, MRI) based on symptoms
    • Metastatic disease management: resection for palliation and potential survival benefit; systemic therapies for stage II–III (adjuvant) and unresectable disease (radiation, immunotherapy, targeted therapy in development)
    • Follow-up: variable schedule, typically 1–4 visits per year with TBSE and lymph node examination; monitor for second primary melanoma; vitamin D status may influence outcomes
    • Breslow depth is measured in micrometers (μm) and is a critical determinant of prognosis and treatment decisions

Adverse Cutaneous Drug Eruptions (ACDEs)

  • Overview:
    • >80 distinct cutaneous drug reaction patterns exist
    • Adverse drug eruptions occur in up to 8% of inpatients; cutaneous reactions are a common ADR target
    • Antibiotics and anticonvulsants are frequent culprits; ~5% of patients on these drug classes develop eruptions
  • Simple vs complex reactions:
    • Simple exanthems (widespread rash) vs Complex drug eruptions including SCARs (Severe Cutaneous Adverse Reactions)
    • SCARs include Toxic Epidermal Necrolysis (TEN), Stevens-Johnson Syndrome (SJS), Staphylococcal Scalded Skin Syndrome (SSSS), Erythema Multiforme, Drug hypersensitivity syndrome, serum sickness-like reaction
  • Risk factors:
    • Female sex; immunosuppression (e.g., HIV)
    • Dermatomyositis; specific HLA alleles associated with drug reactions (examples discussed in guidance)
  • Immunologic pathophysiology:
    • Drugs act as haptens, triggering cell-mediated or humoral immune responses
    • IgE-mediated mechanisms can cause urticaria/angioedema/anaphylaxis
    • Cytotoxic reactions cause petechiae; immune complex reactions cause vasculitis or serum sickness
    • Cell-mediated pathways predominate in many reactions; non-immunologic pathways include predictable dose-dependent toxicity and pharmacologic side effects; interactions or overdose can alter risk
  • Clinical presentation:
    • Red macules or papules, erythema, urticaria, vesicles, pustules or bullae
    • Classic morbilliform exanthem: intertriginous trunk-area involvement, spread to extremities; facial involvement raises concern for systemic involvement
    • Fixed drug eruptions: recurrent patches/plaques at same sites
    • Onset timing: immediate (<1 hour) or delayed (1 hour to 1 week up to 30 days after last dose)
  • Severe reactions (SCAR features):
    • Systemic signs and symptoms: fever, mucosal involvement, organ involvement
    • Cutaneous features: confluent erythema, blisters, epidermal detachment, mucosal erosions, facial edema, skin pain
    • Laboratory clues: eosinophilia, lymphocytosis, leukopenia, abnormal LFTs/renal function
  • Evaluation and testing:
    • Biopsy can help but does not reliably distinguish drug eruptions from viral exanthems or graft-versus-host disease
    • Labs: chemistries (renal/LFTs), CBC, cultures, imaging as indicated
  • Treatment principles:
    • Identify and stop offending medication; educate patient to avoid the culprit and related agents
    • Simple eruptions: self-limited after withdrawal; symptomatic therapy (antihistamines, topical steroids, wound care for bullous eruptions)
    • Severe eruptions: systemic steroids (prednisone) in early phases; IVIg shown in some studies; other systemic therapies (cyclosporine, dexamethasone, TNF inhibitors) have been explored
  • Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)
    • Severity spectrum based on body surface area (BSA) detachment:
    • SJS: < 10% BSA detachment
    • SJS/TEN overlap: 10–30% BSA detachment
    • TEN: > 30% BSA detachment
    • Prodrome: upper respiratory symptoms, fever, mucosal tenderness
    • Pathophysiology: drug-induced immune reaction leading to keratinocyte apoptosis and epidermal necrolysis
    • Common culprits: allopurinol; NSAIDs; antibiotics; aromatic anticonvulsants; onset typically 7–21 days after drug initiation
    • Epidemiology: incidence roughly 1.2–6 per million (SJS) and 0.4–1.2 per million (TEN) per year; higher risk with HIV, immunosuppression, and certain HLA alleles; mortality high in TEN (25–50%)
    • Clinical features: fever, mucosal erosions, target-like lesions, diffuse erythema, painful skin; Nikolsky sign may be positive; ocular, genital mucosa commonly involved; involvement of respiratory tract in many patients
    • Management: urgent withdrawal of offending drug; supportive care in ICU/burn unit; multidisciplinary care (dermatology, ophthalmology, urology); no uniformly proven therapy; IVIg, cyclosporine, steroids, or TNF inhibitors may be used in select cases
    • Approach to treatment and prognosis: early recognition and aggressive supportive care are critical; prognosis correlates with extent of skin detachment and comorbidity

Staphylococcal Scalded Skin Syndrome (SSSS)

  • Also known as Ritter disease
  • Etiology: exfoliative toxins from Staphylococcus aureus cause superficial epidermal split (granular layer)
  • Epidemiology:
    • Most common in young children (<5 years) and neonates; adults with renal impairment or immunocompromise are at higher risk
  • History and presentation:
    • Often preceded by a S. aureus infection; prodrome includes fever, malaise, irritability, cutaneous tenderness
    • Periorificial erythema with superficial blistering; widespread, diffuse erythema; sheets of peeling skin especially on face, trunk, and arms
    • Mucous membranes are usually spared; Nikolsky sign may be positive in affected areas
  • Pathophysiology:
    • Exfoliative toxins induce cleavage within the granular layer of the epidermis
  • Diagnosis:
    • Clinical diagnosis; biopsy not routinely needed; cultures from nasopharynx, conjunctivae, blood may be obtained; blister fluid cultures are often negative for the toxin-producing organism
  • Treatment:
    • Hospitalization with IV anti-staphylococcal antibiotics (e.g., nafcillin/oxacillin, vancomycin, linezolid)
    • Supportive care; avoid nephrotoxic medications; monitor for secondary infections

Nikolsky Sign

  • Positive Nikolsky sign: lateral or tangential pressure on intact skin or mucosa causes epidermal separation and epidermal detachment
  • Helps distinguish certain conditions (e.g., SSSS, SJS/TEN) from other dermatoses
  • Use in assessment: presence of a positive sign supports consideration of SCARs or toxin-mediated processes

Staging and Monitoring: TNM framework and TBSE

  • TNM staging for melanoma (AJCC):
    • T: Tumor thickness/ulceration (Breslow depth important for prognosis)
    • N: Regional lymph node involvement
    • M: Distant metastasis
  • Total body skin examination (TBSE):
    • Essential as part of staging and follow-up for melanoma and other skin cancers
  • Follow-up schedule considerations:
    • Melanoma: follow-up frequency may range from 1–4 visits per year with TBSE and lymph node examination
    • Surveillance for recurrence and second primary skin cancers is part of long-term management

Key Clinical Pearls and Practical Considerations

  • For melanoma detection, use the ABCDE(F) rule and Ugly Duckling sign to guide biopsy decisions and monitor evolution
  • Always consider biopsy for suspicious lesions, especially those with changing color, border irregularity, diameter >6 mm, or evolving characteristics
  • Mohs surgery offers the highest cure rates for select skin cancers and maximal tissue preservation, particularly in cosmetically sensitive or functionally important areas
  • Actinic keratoses should be treated as precancerous lesions given their potential progression to SCC; management includes topical therapies and ablative procedures
  • SJS/TEN require rapid identification and withdrawal of the offending drug, aggressive supportive care, and multidisciplinary management to mitigate mortality risk
  • SSSS presents as widespread blistering with mucosal sparing and requires prompt antibiotic therapy and supportive care; differentiation from other blistering diseases is important

Summary of Treatments by Condition (high-level)

  • Seborrheic keratosis: none required; cosmetic removal if desired; cryosurgery, curettage, shave excision, electrodessication, laser
  • Acrochordon: none required; excision if needed; minor methods for hemostasis
  • Hemangiomas: observation for cherry angiomas; propranolol and laser for severe infantile lesions; observe involution in many cases
  • Lentigines: cosmetic treatments (cryo, laser, peels, bleaching) if desired
  • Melanocytic nevi: observation; excision if suspicious or changes; cosmetic removal
  • Lipoma: observation or excision if symptomatic or bothersome
  • Actinic keratosis: cryotherapy, topical 5-FU, imiquimod, retinoids, chemical peels, surgical excision/biopsy if needed
  • Basal cell carcinoma: excision with margins, ED&C, Mohs; topical therapies for certain low-risk lesions; prevention TBSE annually
  • Squamous cell carcinoma: excision/Mohs, ED&C, topical/intralesional chemotherapy, radiotherapy as indicated
  • Malignant melanoma: surgical excision with margins guided by Breslow depth; potential Mohs in select cases; sentinel node biopsy; imaging as indicated; adjuvant/immunotherapy for certain stages; close follow-up
  • Adverse drug eruptions: stop offending agent; supportive care; systemic therapies (steroids, IVIg, cyclosporine, TNF inhibitors) as indicated; manage SCARs aggressively
  • SSSS: IV antibiotics and supportive care
  • SJS/TEN: aggressive supportive care; multidisciplinary management; variable therapies with limited proven efficacy

Key Numerical References and Formulas (LaTeX)

  • Melanoma precursor risk indicators: lifetime risk roughly rac{1}{48} ext{ to } rac{1}{51}
  • Actinic keratosis progression to SCC: 0.025 ext{ to } 15\%
  • Basal cell carcinoma metastasis: