Differential Diagnosis of Nodules
Introduction
Nodules are palpable, solid lesions greater than 1cm in diameter that extend into the dermis and/or subcutis. They may be inflammatory, infectious, neoplastic (benign or malignant), or depositional. The approach to nodular lesions requires assessment of consistency (soft, firm, hard), mobility, tenderness, surface characteristics, and location. This chapter provides a systematic framework for differential diagnosis.
38.1 Inflammatory Nodules
38.1.1 Erythema Nodosum (EN)
- Definition: Acute panniculitis characterized by tender nodules on the anterior shins.
- Epidemiology: Young women (20-30 years).
- Clinical Features:
- Tender, erythematous, subcutaneous nodules.
- Distribution: Anterior shins (bilateral, symmetric). May occur on thighs, forearms.
- Evolution: Like bruises—Red → Purple → Yellowish-brown (contusiform).
- NO ulceration (distinguishes from nodular vasculitis).
- Course: Self-limited (3-6 weeks). Lesions resolve without scarring or ulceration.
- Histology: Septal panniculitis (inflammation in septa between fat lobules) WITHOUT vasculitis.
- Causes (Mnemonic: "SOBS"):
- Sarcoidosis (Löfgren syndrome: EN + Bilateral hilar lymphadenopathy + Arthritis).
- Oral contraceptives, Pregnancy.
- Bacterial infections (Streptococcal pharyngitis is most common cause, TB, Yersinia, Salmonella).
- Systemic diseases (IBD—Crohn's and UC, Behçet's, Malignancy).
- Drugs (Sulfonamides, Penicillins).
- Idiopathic (up to 50%).
- Workup: ASO titer, CXR (sarcoidosis, TB), Throat culture, Stool culture if GI symptoms, Consider GI evaluation if IBD suspected.
38.1.2 Nodular Vasculitis (Erythema Induratum / Bazin Disease)
- Definition: Lobular panniculitis with vasculitis, associated with tuberculosis or idiopathic.
- Clinical Features:
- Deep, tender nodules on posterior calves.
- MAY ULCERATE (key distinction from EN).
- Chronic, relapsing course.
- Association: Tuberculosis (Bazin's disease). May be tuberculid (reaction to TB antigens without direct infection).
- Histology: Lobular panniculitis with vasculitis.
- Workup: Mantoux/Quantiferon, CXR, PCR for TB.
38.1.3 Panniculitis (Other Causes)
| Type | Distribution | Key Features |
|---|
| Pancreatic Panniculitis | Legs, Abdominal | Associated with pancreatitis, Pancreatic carcinoma. Skin lesions show fat necrosis with "ghost cells." |
| Cold Panniculitis | Cheeks (children) | After ice cream eating or cold exposure. Self-limited. |
| Lupus Panniculitis | Face, Buttocks, Thighs | Associated with DLE. Heals with lipoatrophy (depression). |
| α1-Antitrypsin Deficiency Panniculitis | Lower extremities | Severe ulceration. Associated with liver disease, Emphysema. |
38.2 Infectious Nodules
38.2.1 Sporotrichosis (Nodular Lymphangitis)
- Organism: Sporothrix schenckii (dimorphic fungus).
- Exposure: Gardeners, Florists. Thorns, Sphagnum moss. "Rose gardener's disease."
- Clinical Features:
- Initial papule/nodule at inoculation site → "Sporotrichoid spread" (nodules along lymphatics proximal to primary lesion).
- Nodules may ulcerate.
- Differential for Nodular Lymphangitis: Sporotrichosis, M. marinum, Nocardia, Leishmaniasis, Tularemia.
- Diagnosis: Culture on Sabouraud's agar (room temp shows mold form).
- Treatment: Itraconazole, Potassium iodide (SSKI).
38.2.2 Mycobacterial Infections
M. marinum (Fish Tank Granuloma)
- Exposure: Aquarium keepers, Swimmers, Fish handlers.
- Clinical Features: Nodules on hands/arms at site of minor trauma. May have sporotrichoid spread.
- Diagnosis: Culture at 30-32°C.
- Treatment: Clarithromycin, Doxycycline, Rifampin combinations.
Tuberculous Gumma (Metastatic Tuberculous Abscess)
- Hematogenous spread of TB to skin.
- Subcutaneous "cold" abscess on trunk or extremities.
38.2.3 Deep Fungal Infections
| Infection | Endemic Area | Features |
|---|
| Blastomycosis | North America (Ohio Valley) | Verrucous nodules and plaques. Lung involvement. |
| Histoplasmosis | Ohio/Mississippi Valley | Disseminated in immunocompromised. Papules/Nodules/Ulcers. |
| Cryptococcosis | Worldwide (soil, pigeon droppings) | Umbilicated papules (like molluscum) in AIDS. |
| Coccidioidomycosis | Southwestern US (Valley Fever) | Erythema nodosum common. Nodules/Plaques may appear. |
38.2.4 Cutaneous Leishmaniasis
- Organism: Leishmania species (protozoan).
- Transmission: Sandfly bite.
- Clinical Features: Papule → Nodule → Ulcer with raised border ("volcanic crater").
- Geography: Middle East, Central/South America, Mediterranean.
38.3 Neoplastic Nodules
38.3.1 Benign
| Lesion | Features |
|---|
| Lipoma | Soft, mobile, subcutaneous, "Slippery" feel |
| Epidermal Cyst | Firm, Central punctum, Cheesy content |
| Pilar Cyst | Scalp, No punctum, Firm |
| Dermatofibroma | Firm, Dimple sign positive |
| Pilomatricoma | Rock-hard, Tent sign, Bluish, Children |
| Schwannoma | Along nerve, Tinel's sign |
38.3.2 Malignant
| Lesion | Features |
|---|
| Basal Cell Carcinoma (Nodular) | Pearly papule/nodule with Arborizing telangiectasias, Rolled border, May ulcerate ("Rodent ulcer") |
| Squamous Cell Carcinoma | Indurated nodule, May ulcerate, Sun-exposed areas, Keratotic surface |
| Nodular Melanoma | Rapidly growing pigmented OR amelanotic nodule, Bleeds easily, May have ABCDE features |
| Merkel Cell Carcinoma | Red-violaceous, Rapidly growing, Elderly/Immunocompromised, UV-exposed areas |
| Dermatofibrosarcoma Protuberans | Slowly growing indurated plaque → Protuberant nodules, Fixed, CD34+ |
| Cutaneous Metastases | Multiple, Firm, Skin-colored, History of internal malignancy |
38.3.3 Sister Mary Joseph Nodule
- Definition: Umbilical metastasis from intra-abdominal or pelvic malignancy.
- Significance: Poor prognosis. Common primaries: Gastric, Ovarian, Pancreatic, Colorectal.
38.4 Depositional Nodules
| Cause | Features |
|---|
| Gouty Tophus | White-yellow, Ears/Elbows/Fingers. Urate crystals. Negatively birefringent on polarized microscopy. |
| Rheumatoid Nodules | Firm, Non-tender. Extensor surfaces (Elbows, Knuckles). RF+. |
| Xanthoma (Tuberous/Tendinous) | Yellow-orange. Lipid deposits. Hyperlipidemia. |
| Calcinosis Cutis | Hard, Calcium deposits. Scleroderma, Dermatomyositis. |
38.5 Diagnostic Algorithm
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38.6 Summary Comparison Table
| Category | Examples | Key Features |
|---|
| Inflammatory | EN, Nodular Vasculitis | Tender, Anterior shins / Posterior calves |
| Infectious | Sporotrichosis, M. marinum | Lymphangitic spread, Exposure history |
| Benign Neoplastic | Lipoma, Cyst, Dermatofibroma, Pilomatricoma | Mobile, Punctum, Dimple/Tent sign |
| Malignant Neoplastic | BCC, SCC, Melanoma, Merkel | Pearly, Ulceration, Rapid growth |
| Depositional | Gout, Rheumatoid, Xanthoma | Specific locations, Metabolic associations |
38.7 Clinical Pearls
- Tender nodules on anterior shins → Erythema Nodosum. Get CXR (sarcoidosis, TB), ASO titer (Strep).
- Posterior calf nodules that ulcerate → Nodular vasculitis. Consider TB workup (Mantoux, Quantiferon).
- Nodules along lymphatics + Gardener/Florist → Sporotrichosis. Culture, treat with Itraconazole.
- Soft, mobile, subcutaneous nodule → Lipoma. Benign.
- Pearly nodule + Arborizing vessels → BCC. Excise.
- Rapidly growing pigmented or pink nodule → Nodular melanoma. URGENT biopsy.
- White nodule on ear/elbow + Hyperuricemia → Gouty tophus. Urate-lowering therapy.
- Umbilical nodule → Sister Mary Joseph nodule. Investigate for GI/Pelvic malignancy.