A 70-year-old man comes to the physician because of a painless skin lesion on his neck for the past 5 months. The lesion has gradually become darker in color and is often pruritic. He has a similar lesion on the back. He is a retired landscaper. He has smoked half a pack of cigarettes daily for 45 years. Physical examination shows a 0.9-cm hyperpigmented papule on the neck with a greasy, wax-like, and stuck-on appearance. Histopathologic examination is most likely to show which of the following?

Immature keratinocytes with small keratin-filled cysts

Nests of melanocytes at the base of rete ridges and the dermis

Fibroblast proliferation with small, benign dermal growth

S100-positive epithelioid cells with fine granules in the cytoplasm

Koilocytes in the granular cell layer of the epidermis

A 65-year-old woman presents to a dermatology clinic complaining about a couple of well-demarcated, dark, round skin lesions on her face. She claims she has had these lesions for 3 or 4 years. The lesions are painless, not pruritic, and have never bled. However, she is moderately distressed about the potential malignancy of these lesions after she heard that a close friend was just diagnosed with a melanoma. The medical history is unremarkable. Physical examination reveals a few well-demarcated, round, verrucous lesions, with a stuck-on appearance, distributed on the patient's back and face (see image). Under a dermatoscope, the lesions showed multiple comedo-like openings, milia cysts, and a cerebriform pattern. What is the best next step of management?

Reassure the patient and provide general recommendations

A 48-year-old man is brought to the emergency department with a stab wound to his chest. The wound is treated in the emergency room. Three months later he develops a firm 4 x 3 cm nodular mass with intact epithelium over the site of the chest wound. On local examination, the scar is firm, non-tender, and there is no erythema. The mass is excised and microscopic examination reveals fibroblasts with plentiful collagen. Which of the following processes is most likely related to the series of events mentioned above?

Foreign body response from suturing

Poor wound healing from diabetes mellitus

A 41-year-old male who takes NSAIDs regularly for his chronic back pain develops severe abdominal pain worse with eating. Upper endoscopy is performed and the medical student asks the supervising physician how the histological differentiation between a gastric ulcer and erosion is made. Which of the following layers of the gastric mucosa MUST be breached for a lesion to be considered an ulcer?

Epithelium, lamina propria, muscularis mucosa

Epithelium, lamina propria, muscularis mucosa, submucosa, and adventitia

Epithelium, lamina propria, muscularis mucosa, and submucosa

A 50-year-old woman with rheumatoid arthritis on methotrexate develops rapidly progressive painful ulcers on her legs with violaceous undermined borders. Biopsy shows neutrophilic dermal infiltrate with areas of necrosis, but no vasculitis or infection. Wound cultures are negative. Despite debridement, the ulcers worsen. C-ANCA and P-ANCA are negative. Evaluate the diagnosis and determine the management that addresses both the cutaneous condition and systemic disease.

Continue methotrexate, add TNF-alpha inhibitor and systemic corticosteroids

Discontinue all immunosuppression to allow wound healing

Increase methotrexate dose and add wound care

Discontinue methotrexate, start cyclosporine and prednisone

Start broad-spectrum antibiotics and surgical debridement

A 25-year-old woman presents with painful oral ulcers and a pustular rash at venipuncture sites. She has genital ulcers and a history of recurrent uveitis. Skin biopsy from a pustule shows neutrophilic infiltrate in the dermis without vasculitis or infection. HLA-B51 testing is positive. She is planning pregnancy. Evaluate the management strategy considering disease control and pregnancy planning.

Start infliximab, use contraception, then transition to low-risk therapy before conception

Start methotrexate for disease control

Start colchicine monotherapy and proceed with pregnancy

Start high-dose corticosteroids and azathioprine, delay pregnancy

Avoid all immunosuppression and manage symptoms only

Benign epithelial tumors for USMLE Step 3: High-Yield Pathology Lessons

Keratoses - Stuck-On Old Warts

Seborrheic Keratosis (SK): Common, benign epidermal tumors in older adults.
- Clinical: "Stuck-on," waxy, well-demarcated papules/plaques; color varies (tan to black).
- Histology: Exophytic proliferation of basaloid cells, keratin-filled invaginations (horn cysts), and pseudohorn cysts.
- Variants:
  - Dermatosis Papulosa Nigra (DPN): Multiple small, hyperpigmented papules on the face/neck of darker-skinned individuals (e.g., Fitz IV-VI).
  - Stucco Keratosis: Small, white-gray papules on lower extremities; "stuck-on" dry appearance.

Seborrheic Keratosis: Clinical Presentation

⭐ The sudden eruptive appearance of multiple seborrheic keratoses, known as the sign of Leser-Trélat, can be a cutaneous marker for internal malignancy (e.g., gastric adenocarcinoma).

Acanthosis Nigricans - Velvet Clues Within

Pathophysiology: A disorder of keratinocyte proliferation, often driven by ↑ insulin levels or fibroblast growth factor receptor 3 (FGFR3) activation. Insulin binds to IGF-1 receptors on keratinocytes, stimulating their growth.
Presentation: Symmetric, velvety, hyperpigmented plaques.
Locations: Commonly found in flexural areas like the axillae, groin, and posterior neck.

Acanthosis Nigricans with Skin Tags in Axilla

Types:
- Benign: Associated with obesity, insulin resistance, and endocrine disorders (e.g., PCOS, diabetes).
- Malignant: A paraneoplastic sign, often linked to underlying GI malignancies (especially gastric adenocarcinoma).

⭐ High-Yield: Sudden, explosive onset of acanthosis nigricans in an older, non-obese patient is a red flag for an internal malignancy.

Keratinocyte Tumors - Sun's Angry Children

Sun-induced epithelial lesions with malignant potential, often on sun-exposed skin (face, hands). 📌 Mnemonic: Actinic Keratosis for Atypical Keratinocytes.

Feature	Actinic Keratosis (AK)	Keratoacanthoma (KA)
Clinical	Sandpaper-like, erythematous patch/papule	Rapidly growing, dome-shaped nodule with central keratin plug
Progression	Premalignant; <1%/year risk of SCC	Often regresses; variant of well-differentiated SCC
Histology	Basal cell atypia, parakeratosis, solar elastosis	Symmetrical, crateriform; glassy eosinophilic keratinocytes

⭐ Keratoacanthoma's classic presentation is a rapidly growing "volcano-like" nodule with a central keratin-filled crater, which may spontaneously involute.

Adnexal Neoplasms - Sweat & Hair Glitches

Benign tumors from sweat glands or hair follicles, often presenting as skin-colored papules.

Tumor	Origin	Clinical Presentation	Histology
Syringoma	Eccrine	Multiple, small periorbital papules	Ducts with "tadpole" or comma shapes
Cylindroma	Apocrine	Scalp/forehead nodules ("Turban tumor")	"Jigsaw puzzle" pattern of basaloid islands
Trichoepithelioma	Follicular	Flesh-colored facial papules	Basaloid islands, abortive follicles, horn cysts

⭐ Brooke-Spiegler syndrome is an autosomal dominant condition featuring multiple cylindromas and trichoepitheliomas, caused by a CYLD gene mutation.

High‑Yield Points - ⚡ Biggest Takeaways

Seborrheic keratosis presents as waxy, "stuck-on" papules; the Leser-Trélat sign (sudden eruptive onset) suggests underlying GI adenocarcinoma.

Acanthosis nigricans manifests as velvety, hyperpigmented plaques in flexural areas, strongly associated with insulin resistance or malignancy.

Keratoacanthoma is a rapidly growing, dome-shaped nodule with a central keratin-filled crater that may spontaneously resolve.

Epidermal inclusion cysts are common subcutaneous nodules with a central punctum, containing degenerating keratin.

Cylindromas are scalp "turban tumors" showing a "jigsaw puzzle" pattern of basaloid islands on histology.

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