Cutaneous Malignancies, Soft Tissue Infections & Viral Exanthems

Compare the two non-melanoma keratinocyte skin cancers: (1) Basal Cell Carcinoma (BCC) is the most common malignancy in humans, arising from basal epidermal cells on chronic sun-exposed skin (upper lip, nose, periorbital face, ears; driven by sporadic or germline PTCH1 / Hedgehog signaling pathway mutations [autosomal dominant Gorlin Basal Cell Nevus Syndrome]). Classic Nodular BCC presents as a slow-growing, pearly or translucent flesh-colored papule/nodule with rolled borders, surface arborizing TELANGIECTASIAS, and central ulceration ('rodent ulcer') that crusts and bleeds easily. Histopathology shows islands of darkly staining basaloid cells with peripheral 'PALISADING' nuclei (nuclei lined up like fence posts at the edge of the nest) and peritumoral stromal retraction clefts. BCC rarely metastasizes (<0.1%) but is locally destructive; treat high-risk facial/recurrent BCC with Mohs Micrographic Surgery (highest cure rate and tissue sparing!) or standard surgical excision (4-mm margins) / Electrodesiccation and Curettage for low-risk truncal lesions (advanced/unresectable BCC is treated with Hedgehog inhibitor Vismodegib). (2) Cutaneous Squamous Cell Carcinoma (SCC) is the #2 skin cancer overall—and the #1 skin cancer in Solid-Organ Transplant Recipients (65× increased risk on calcineurin/azathioprine immunosuppression!) and in darker-skinned patients—arising on sun-exposed sites (LOWER lip, dorsal hands, scalp, pinna) from its obligate premalignant precursor, Actinic Keratosis (gritty, sandpaper-like erythematous scaly papules treated with topical 5-Fluorouracil, Imiquimod, or Liquid Nitrogen Cryotherapy; SCC in situ restricted to the full epidermis is Bowen Disease). Invasive SCC presents as an ulcerated, hyperkeratotic, scaly erythematous nodule or plaque that never heals; also watch for Marjolin Ulcer (aggressive SCC arising decades later inside a chronic burn scar, osteomyelitis sinus tract, or venous stasis ulcer!) and Keratoacanthoma (a dome-shaped nodule with a central keratin plug that grows explosively over 4–6 weeks). Biopsy shows atypical keratinocytes invading the dermis with eosinophilic concentric 'KERATIN PEARLS' and intercellular bridges.

Malignant Melanoma arises from neural crest-derived epidermal melanocytes (positive for S-100, HMB-45, and Melan-A/MART-1 on immunohistochemistry) and is screened clinically using the ABCDE Criteria: Asymmetry, Border irregularity, Color variegation (shades of black, brown, blue, red, or white regression), Diameter >6 mm, and Evolving size/shape/symptoms (plus the 'Ugly Duckling' sign). Memorize the four clinicopathologic subtypes: (1) Superficial Spreading Melanoma (#1 subtype, 70%: BRAF-driven radial growth phase across the back in men and legs in women before vertical invasion); (2) Nodular Melanoma (#2 subtype, worst early prognosis because it skips the radial growth phase and plunges immediately into a vertical growth phase); (3) Lentigo Maligna Melanoma (slow-growing precursor in situ on the chronically sun-damaged face of elderly patients); and (4) Acral Lentiginous Melanoma (arising on the palms, soles, and subungual nail beds [Hutchinson sign: pigment extending onto the proximal nail fold]—the #1 subtype in African American, Asian, and Hispanic patients, completely unrelated to UV sun exposure!). THREE MANDATORY MELANOMA BOARD RULES: Rule 1: When melanoma is suspected, perform a Full-Thickness Excisional Biopsy with 1–3 mm clinical margins extending into the subcutaneous fat (NEVER perform a superficial shave biopsy, because shave biopsy transects the base of the tumor and destroys the ability to measure tumor depth!). Rule 2: The #1 most important prognostic factor for survival and metastasis in Melanoma is BRESLOW THICKNESS (depth of invasion in millimeters measured from the granular layer of the epidermis to the deepest invasive melanoma cell; if Breslow thickness is ≥0.8–1.0 mm [or <0.8 mm with ulceration], perform a Sentinel Lymph Node Biopsy alongside wide local excision [1-cm margin for ≤1 mm depth; 2-cm margin for >2 mm depth]). Rule 3: Approximately 50% of melanomas harbor an activating BRAF V600E mutation (treated in metastatic disease with combined BRAF Inhibitor [Vemurafenib/Dabrafenib] + MEK Inhibitor [Cobimetinib/Trametinib] or first-line Immune Checkpoint Inhibitors: Anti-PD-1 [Nivolumab, Pembrolizumab] + Anti-CTLA-4 [Ipilimumab]).

Match the anatomical layer of the skin to the causative Gram-positive organism and antibiotic regimen: (1) Impetigo is a contagious infection of the superficial epidermis in children: Non-Bullous Impetigo (80%) (caused by Staphylococcus aureus or Streptococcus pyogenes entering minor bug bites/abrasions) presents with vesicles/pustules that rupture into pathognomonic 'Honey-Colored Crusts' on the face/perioral skin (and can be followed 3–6 weeks later by Post-Streptococcal Glomerulonephritis [PSGN], though impetigo never causes Acute Rheumatic Fever!), whereas Bullous Impetigo (caused by S. aureus Exfoliative Toxin A locally cleaving Desmoglein-1) presents with flaccid bullae and collarettes of scale. Treat localized impetigo with Topical Mupirocin (or Retapamulin), and widespread impetigo with oral Cephalexin. (2) Erysipelas is a non-purulent infection of the SUPERFICIAL DERMIS and dermal lymphatics caused almost exclusively by Group A Streptococcus pyogenes, presenting with abrupt high fever/chills and a bright, fiery-red, indurated plaque with SHARPLY DEMARCATED, RAISED, ADVANCING BORDERS on the lower legs or butterfly malar face (treat with Penicillin V, Amoxicillin, or Cefazolin/Ceftriaxone). (3) Non-Purulent Cellulitis infects the DEEP DERMIS and subcutaneous fat (caused most commonly by beta-hemolytic Streptococci [S. pyogenes] > MSSA, entering via interdigital tinea pedis [athlete's foot] maceration or saphenous vein harvest sites), presenting with warm, tender, erythematous swelling with ILL-DEFINED, indistinct borders; treat uncomplicated non-purulent cellulitis with a beta-lactam targeting Strep/MSSA (Oral Cephalexin, Dicloxacillin, or IV Cefazolin). Conversely, Purulent SSTIs (Cutaneous Abscess, Furuncle, Carbuncle) are caused predominantly by Community-Acquired MRSA: the primary treatment for any cutaneous abscess is Incision and Drainage (I&D), plus oral MRSA-active antibiotics (TMP-SMX, Doxycycline, or Clindamycin; IV Vancomycin, Daptomycin, or Linezolid for systemic toxicity).

Never miss the two deep soft-tissue surgical emergencies on board exams: (1) Necrotizing Fasciitis is a fulminant, rapidly spreading infection of the deep fascia and subcutaneous tissue (tracking along avascular fascial planes at 2–3 cm/hour while initially sparing the overlying skin!) classified into Type I (Polymicrobial aerobic/anaerobic flora: Bacteroides, Clostridium, Enterobacteriaceae, Streptococci—classic in diabetic foot ulcers, perirectal abscesses, or Fournier Gangrene of the perineum/scrotum [also associated with SGLT2 inhibitors!]) and Type II (Monomicrobial Streptococcus pyogenes [Group A Strep] or MRSA in healthy hosts after minor trauma/varicella, driven by streptococcal pyrogenic exotoxins / superantigens causing Toxic Shock Syndrome). Memorize the Cardinal Red Flags of Necrotizing Fasciitis: (a) SEVERE PAIN OUT OF PROPORTION TO PHYSICAL EXAM FINDINGS (the earliest and most sensitive clue!), progressing later to cutaneous ANESTHESIA as thrombosis of perforating nutrient vessels infarcts cutaneous nerves; (b) Rapidly spreading woody edema extending beyond the margins of erythema, violaceous hemorrhagic bullae, skin necrosis, and subcutaneous CREPITUS (gas on X-ray/CT); and (c) Systemic Septic Shock, high fever, lactic acidosis, hyponatremia, and WBC >15,000/μL. CRITICAL BOARD RULE: When Necrotizing Fasciitis is suspected clinically, DO NOT DELAY SURGERY TO OBTAIN CT OR MRI IMAGING—proceed IMMEDIATELY to the Operating Room for Emergent Surgical Exploration and Wide Radical Debridement PLUS empiric broad-spectrum IV antibiotics: Vancomycin (or Linezolid) + Piperacillin-Tazobactam (or Meropenem) + CLINDAMYCIN (Clindamycin is mandatory because it binds the 50S ribosomal subunit to shut down bacterial exotoxin and superantigen synthesis independent of bacterial growth phase [Eagle effect]!). (2) Clostridial Myonecrosis (Gas Gangrene) is caused by Clostridium perfringens (a spore-forming, Gram-positive anaerobic rod inoculated into deep traumatic crush/gunshot wounds or septic abortions) which secretes Alpha-Toxin (Lecithinase / Phospholipase C)—degrading cell membrane phospholipids to cause rapid skeletal muscle necrosis, foul-smelling serosanguinous ('dishwater') exudate with abundant gas bubbles/crepitus, massive intravascular hemolysis, and shock (Gram stain of wound fluid shows large Gram-positive rods with a Striking Absence of Neutrophils [PMNs] because alpha-toxin lyses leukocytes; treat with Emergent Surgical Debridement + IV Penicillin G + Clindamycin).

Management of a suspicious pigmented lesion always proceeds in two distinct surgical steps. Step 1 (Diagnostic Biopsy): Perform a full-thickness excisional biopsy with narrow 1–3 mm clinical margins extending into the subcutaneous fat (never perform a wide 1–2 cm excision before pathology confirms melanoma, and never perform a superficial shave biopsy that transects the base). Step 2 (Definitive Wide Local Excision): Once pathology reports the exact Breslow depth, return to the operating room for wide local excision: 0.5 cm margin for melanoma in situ; 1.0 cm margin for Breslow ≤1.0 mm; 1.0–2.0 cm margin for Breslow 1.01–2.0 mm; and 2.0 cm margin for Breslow >2.0 mm (margins exceeding 2.0 cm do not improve survival).

Roughly 50% of cutaneous melanomas harbor an activating point mutation in the serine-threonine kinase BRAF (V600E), which constitutively activates the MAPK/ERK proliferation pathway. In patients with unresectable or metastatic BRAF V600E-mutant melanoma, targeted therapy ALWAYS combines a BRAF inhibitor (vemurafenib, dabrafenib, encorafenib) with a MEK inhibitor (cobimetinib, trametinib, binimetinib); combining MEK blockade delays acquired resistance and prevents paradoxical secondary cutaneous squamous cell carcinomas induced by BRAF-inhibitor monotherapy. First-line immunotherapy utilizes PD-1 inhibitors (pembrolizumab, nivolumab) alone or combined with the CTLA-4 inhibitor ipilimumab.

When amelanotic or metastatic melanoma mimics poorly differentiated carcinoma or sarcoma on H&E histology, immunohistochemistry confirms melanocytic lineage via positive staining for S-100 (most sensitive), SOX10, HMB-45, and Melan-A (MART-1). Familial atypical mole and melanoma syndrome is driven by germline mutations in the tumor suppressor gene CDKN2A (encoding p16^INK4a), which normally inhibits CDK4/6 and is also strongly associated with familial pancreatic adenocarcinoma.

Mohs Micrographic Surgery involves sequential horizontal frozen-section mapping of 100% of the peripheral and deep surgical margins while maximally sparing normal adjacent tissue. Mohs is the gold-standard treatment of choice for BCC and SCC when lesions are located in cosmetically and functionally critical 'H-zone' facial areas (periorbital, eyelids, nose, nasolabial folds, lips, ears), as well as for recurrent tumors, tumors >2 cm, aggressive histologic subtypes (morpheaform/sclerosing BCC or perineural SCC), and lesions in immunosuppressed patients. Standard low-risk trunk or extremity BCC/SCC is treated with simple elliptical excision (4 mm margins) or electrodessication and curettage.

Invasive Squamous Cell Carcinoma breaches the dermal basement membrane as irregular nests of eosinophilic polygonal keratinocytes producing concentric laminated whorls of keratin (keratin pearls). When SCC arises decades later within a chronic non-healing thermal burn scar, chronic osteomyelitis sinus tract, or venous stasis ulcer, it is termed a Marjolin ulcer—a highly aggressive subtype with a high rate of regional lymph node metastasis requiring wide surgical excision. Full-thickness intraepidermal SCC in situ (Bowen disease; or Erythroplasia of Queyrat when presenting as a velvety red plaque on the uncircumcised glans penis) has not yet invaded the dermis.

Board examinations frequently test four classic paraneoplastic skin eruptions: (1) Sign of Leser-Trélat (abrupt explosion of multiple Seborrheic Keratoses → Gastric or Colorectal Adenocarcinoma); (2) Acanthosis Nigricans (velvety hyperpigmented plaques in axillae/neck; usually benign insulin resistance in obesity/PCOS, but sudden onset in a non-obese older adult with palmar tripe palms signals Gastric Adenocarcinoma); (3) Necrolytic Migratory Erythema (erythematous blistering plaques on perineum/perioral/lower extremities → pancreatic alpha-cell Glucagonoma); and (4) Sweet Syndrome (acute febrile neutrophilic dermatosis with tender juicy red plaques → Acute Myeloid Leukemia [AML]).

Both Bullous Impetigo and Staphylococcal Scalded Skin Syndrome (SSSS) are mediated by Staphylococcus aureus Exfoliative Toxins A and B, which act as serine proteases that cleave Desmoglein-1 solely within the superficial stratum granulosum (repeating the exact molecular target of Pemphigus Foliaceus). In Bullous Impetigo, toxin remains localized at the infection site, producing intact flaccid bullae filled with bacteria and neutrophils. In SSSS (occurring in neonates and young children from an umbilical or nasopharyngeal focus), toxin disseminates hematogenously, causing diffuse tender scarlatiniform erythema, perioral crusting, sterile intraepidermal sloughing (positive Nikolsky sign), and complete sparing of the oral/ocular mucosae (distinguishing SSSS from TEN!). Treat SSSS with IV nafcillin/oxacillin or vancomycin.

Specific environmental or animal exposures point to classic board pathogens: (1) Dog or Cat bite developing rapid cellulitis within <24 hours → Pasteurella multocida (Gram-negative coccobacillus; treat with Amoxicillin-Clavulanate); (2) Cat scratch developing regional tender lymphadenopathy 1–2 weeks later (or Bacillary Angiomatosis vascular papules in HIV with CD4 <100, mimicking Kaposi sarcoma but containing neutrophils vs. HHV-8 spindle cells) → Bartonella henselae (Warthin-Starry stain; treat with Azithromycin or Doxycycline); (3) Saltwater / raw oysters in a patient with cirrhosis or hemochromatosis developing rapidly progressive hemorrhagic bullous cellulitis and septic shock → Vibrio vulnificus (treat with Doxycycline plus Ceftriaxone).

Verruca vulgaris (common warts on hands/knees caused by HPV 1, 2, 4) present as hyperkeratotic papules with thrombosed dermal capillaries (black dots on paring) and koilocytes, treated with salicylic acid or cryotherapy. Contrast this with Molluscum Contagiosum (caused by a double-stranded DNA Poxvirus), which presents in children, wrestlers, or sexually active adults as flesh-colored, dome-shaped papules with central umbilication; histology demonstrates large eosinophilic cytoplasmic viral inclusions (Henderson-Paterson / molluscum bodies).

Vascular skin neoplasms are high-yield board favorites: (1) Infantile (Strawberry) Hemangioma is a benign capillary endothelial tumor (GLUT1-positive) that appears in the first weeks of life, grows rapidly during the first 6–12 months, and spontaneously involutes by age 5–9 years (if periorbital/airway-obstructing or ulcerated, treat with oral Propranolol). (2) Cherry Hemangioma is the most common benign vascular proliferation in older adults, appearing as bright ruby-red 1–5 mm papules on the trunk that do not regress. (3) Glomus Tumor is a benign but exquisitely painful, cold-sensitive blue-red subungual nodule arising from the modified smooth muscle cells of the thermoregulatory glomus body (arteriovenous shunt) beneath the fingernail bed.

In an HIV-positive patient with CD4⁺ count <100 cells/mm³ presenting with violaceous, vascular-appearing cutaneous papules and plaques, histology separates two classic mimics: Kaposi Sarcoma is an endothelial malignancy caused by Human Herpesvirus-8 (HHV-8) that shows spindle cells, slit-like vascular spaces, extravasated RBCs, and lymphocytic infiltrate (treated with antiretroviral therapy plus liposomal doxorubicin). Conversely, Bacillary Angiomatosis is a bacterial infection caused by Bartonella henselae (from a cat scratch) that shows lobular capillary proliferation with a dense neutrophilic infiltrate and clumps of Warthin-Starry silver-staining bacilli (cured with oral erythromycin or doxycycline).

When a board vignette describes an infant presenting with brief, symmetric jackknife flexion jerks of the neck, trunk, and extremities (Infantile Spasms / West Syndrome) with chaotic high-voltage slow waves and multifocal spikes on EEG (hypsarrhythmia), immediately examine the skin with a Wood lamp for hypopigmented ash-leaf macules and order an echocardiogram for a cardiac rhabdomyoma to confirm Tuberous Sclerosis. While ACTH is first-line for idiopathic West syndrome, Vigabatrin (an irreversible GABA transaminase inhibitor; adverse effect: permanent concentric visual field constriction) is the specific drug of choice for infantile spasms caused by Tuberous Sclerosis.