Differential Diagnosis of Palpable Lesions: Overview

Introduction

Palpable cutaneous lesions—those that can be felt as elevated above the skin surface—encompass an enormous range of conditions from benign cysts to malignant tumors. A systematic approach based on color, consistency, and location allows efficient differential diagnosis. This chapter provides the framework for subsequent detailed chapters on specific palpable lesion types.

29.1 Initial Assessment of Palpable Lesions

29.1.1 Key Questions to Ask

How long has it been present? (Congenital vs. Acquired, Rapidly growing vs. Stable)
Is it painful? (Painful tumors: LEND AN EGG mnemonic)
Has it changed? (Growth, Color change, Bleeding)
Any associated symptoms? (Pruritus, Discharge, Systemic symptoms)
Family history? (Neurofibromatosis, Familial syndromes)

29.1.2 Physical Examination Approach

Size: Measure in two dimensions.
Shape: Round, Oval, Sessile, Pedunculated.
Color: Skin-colored, Pigmented, Erythematous, Yellow, White.
Consistency: Soft, Firm, Hard, Cystic/Fluctuant.
Mobility: Mobile vs. Fixed to underlying structures.
Surface: Smooth, Verrucous, Umbilicated, Ulcerated.
Tenderness: Painful or non-painful.

29.2 Classification by Color

Color	Implications	Common Examples
Skin-Colored	Keratinocytic, Adnexal, Cystic, Deep dermal/Subcutaneous	Epidermal cyst, Lipoma, Dermatofibroma, Neurofibroma, Warts
Pigmented (Brown/Black)	Melanocytic or Melanin-containing	Melanocytic nevi, Melanoma, Seborrheic keratosis, Pigmented BCC
White	Keratin, Calcium, Urate, Mucin deposits	Milia, Calcinosis cutis, Gouty tophus
Yellow	Lipid deposition, Sebaceous	Xanthomas, Sebaceous hyperplasia, Juvenile xanthogranuloma
Red/Vascular	Vascular proliferation or Inflammation	Hemangioma, Pyogenic granuloma, Cherry angioma, Kaposi sarcoma
Blue	Deep melanin or Vascular	Blue nevus, Venous malformation, Blue rubber bleb nevus
Translucent/Pearly	BCC characteristic	Basal cell carcinoma

29.3 Classification by Consistency/Texture

Consistency	Mechanism	Examples
Soft/Compressible	Fat, Vascular spaces	Lipoma, Hemangioma, Neurofibroma ("buttonhole" sign)
Firm/Rubbery	Fibrous tissue, Dermal	Dermatofibroma, Keloid, Scar tissue
Hard/Stony	Calcium, Bone, Cartilage	Calcinosis, Pilomatricoma ("tent sign"), Osteoma cutis
Cystic/Fluctuant	Fluid within sac	Epidermal cyst, Ganglion, Cystic hygroma

29.4 Special Clinical Signs for Palpable Lesions

29.4.1 Dimple Sign

Technique: Lateral compression of the lesion produces central dimpling (invagination).
Classic Example: Dermatofibroma. The lesion puckers inward when squeezed.
Significance: Indicates dermal tethering. Distinguishes dermatofibroma from other firm nodules.

29.4.2 Buttonhole Sign

Technique: Firm pressure causes the lesion to invaginate into the skin (as if through a buttonhole).
Classic Example: Neurofibroma. The soft tumor can be pushed into the dermis.
Significance: Indicates a soft, non-encapsulated dermal tumor.

29.4.3 Tent Sign (Teepee Sign)

Technique: Stretching the overlying skin reveals sharp, angular facets.
Classic Example: Pilomatricoma. The hard, calcified tumor creates angular projections.
Significance: Indicates a hard, often calcified, subcutaneous lesion.

29.4.4 Transillumination

Technique: Shine a penlight through the lesion in a dark room.
Positive: Light passes through → Cystic/Fluid-filled (Cystic hygroma, Ganglion cyst).
Negative: Light blocked → Solid lesion.

29.4.5 Umbilication

Definition: Central depression or dell.
Examples:
- Molluscum Contagiosum: Umbilicated papules.
- Keratoacanthoma: Crateriform with central keratin plug.
- Sebaceous Hyperplasia: Central umbilication with "crown vessels."

29.5 Painful Cutaneous Tumors: "LEND AN EGG"

A classic mnemonic for tumors that are typically painful on palpation:

Letter	Tumor	Key Features
L	Leiomyoma (Piloleiomyoma)	Firm papule, Contracts with cold, Often multiple
E	Eccrine Spiradenoma	Solitary, Deep dermal nodule, Blue-red
N	Neuroma (Traumatic)	Post-amputation or at scar sites
D	Dermatofibroma (sometimes)	Typically non-painful but can be tender
A	Angiolipoma	Lipoma-like but painful, Forearm common
N	Neurilemmoma (Schwannoma)	Encapsulated, Mobile, Along nerve course
E	Endometrioma (Cutaneous)	Umbilical or scar site, Cyclic pain with menses
G	Glomus Tumor	Subungual, Exquisite pain with pressure/cold
G	Granular Cell Tumor	Firm, Tongue or skin, Often misdiagnosed

[!TIP] Subungual painful nodule + Exquisite tenderness to cold/pressure = Glomus Tumor

29.6 Approach by Location

Certain lesions have predilection for specific sites:

Location	Common Lesions
Scalp	Pilar cyst, Cylindroma, Sebaceous nevus
Face	Sebaceous hyperplasia, Trichoepithelioma, Syringoma (eyelids), BCC
Neck	Thyroglossal cyst, Branchial cyst, Lipoma
Trunk	Lipoma, Epidermal cyst, Dermatofibroma
Extremities	Dermatofibroma (legs), Ganglion (wrist/foot), Pilomatricoma (arms in children)
Subungual	Glomus tumor, Subungual exostosis, Melanoma
Genital	Epidermoid cyst, Bartholin cyst, Fordyce spots

29.7 Master Algorithm: Approach to Palpable Lesions

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29.8 Summary Table: Quick Reference

Category	Examples	Key Differentiating Sign
Skin-Colored	Lipoma, Cyst, Dermatofibroma, Neurofibroma, Wart	Dimple sign, Buttonhole sign, Punctum
Pigmented	Nevus, Melanoma, Seborrheic keratosis, Blue nevus	ABCDE criteria, Dermoscopy
White	Milia, Calcinosis, Gouty tophus	Size, Hardness, Location
Yellow	Xanthoma, Sebaceous hyperplasia, JXG	Lipid association, Umbilication
Red/Vascular	Hemangioma, Pyogenic granuloma, Lichen planus	Friability, Blanching, Morphology

29.9 Clinical Pearls

Firm papule on leg + Dimple sign → Dermatofibroma. Benign.
Soft tumor + Buttonhole sign → Neurofibroma. If multiple, consider NF1.
Subungual painful nodule + Exquisite cold sensitivity → Glomus tumor.
Child + Hard subcutaneous nodule + Tent sign → Pilomatricoma.
Changing pigmented papule → Melanoma until proven otherwise. Biopsy.
Yellow crops on buttocks → Eruptive xanthoma. Check triglycerides urgently.
Friable red nodule that bleeds easily → Pyogenic granuloma. Also rule out amelanotic melanoma.