Squamous cell carcinoma of the skin differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Roukoz A. Karam, M.D.[2] Homa Najafi, M.D.[3]

Overview

Squamous cell carcinoma should be differentiated from melanoma and basal cell carcinoma. It accounts for 20% of all non-melanomatous tumors and is fairly invasive contrary to its counterpart, basal cell carcinoma. Squamous cell carcinoma typically presents as a non-healing ulcer or growth on a sun-exposed area of the skin.

Differentiating Squamous cell carcinoma from other Diseases

A few conditions that mimic Squamous cell carcinoma of the skin include the following:

Diseases		Skin examination					Diagnosis		Additional findings
		Type	Color	Texture	Size	Distribution	Dermoscopic Findings	Histopathology
Cutaneous squamous cell carcinoma	SCC in situ (Bowen's disease)	Patch Plaque	Erythematous Skin colored	Scaly	Variable	Fair-skinned individuals: sun-exposed areas In black individuals: legs, anus, and areas of chronic inflammation	Presence of dotted and/or glomerular vessels White to yellowish surface scales Red-yellowish background	Keratinocytic dysplasia of the epidermis No infiltration into dermis Pleomorphic keratinocytes Hyperchromatic nuclei	Slow growth over the years
	Invasive squamous cell carcinoma	Papule Plaque Nodule	Skin colored	Indurated + hyperkeratotic (well differentiated) Soft + ulceration (poorly differentiated)	0.5 to 1.5 cm	Fair-skinned individuals: sun-exposed areas In black individuals: legs, anus, and areas of chronic inflammation	White circles White structureless areas Masses of keratin Hairpin and linear-irregular vessels	Keratinocytic dysplasia of the epidermis No infiltration into dermis Pleomorphic keratinocytes Hyperchromatic nuclei	May be painful or pruritic
Keratoacanthoma		Macule Papule May have telangiectasias	Skin-colored Mildly erythematous	Prominent keratinous core in the center of the nodule	1 to 2.5 cm	Sun-exposed areas Face, neck, hands, and arms	White circles Keratin Blood spots White structureless zones	Well-differentiated squamous epithelium Central keratin core Epidermal hyperplasia + large eosinophilic keratinocytes Dermal inflammatory infiltrate	Rapid growth (within weeks)
Dermatofibroma		Nodule	Hyperpigmented	Firm	0.3- 1 cm	Mostly seen in extremities		Localized nodular proliferation of spindle-shaped fibrous cells in a mixture of histocytoid cells inside the dermis Spiculated margin of cells “Storiform” pattern Collagen bundles "Grenz zone" Epidermal hyperplasia	Slow growth over the years
dermatofibrosarcoma protuberans		Patch Plaque	Skin-colored, violet or reddish-brown	Firm	1-5 cm	Mostly seen in trunk	Presence of vessels pigmented network pinkish background	Highly cellular with cells having following characteristics: Monomorphic Thin Spindly Scant eosinophilic cytoplasm Hyperchromatic nuclei (resembling neurofibroma)
Kaposi sarcoma		Macule Patch	Red/violaceous	Smooth	Variable	Mucus membrane	Rainbow pattern scaly surface Small brown globules	Spindle cells with minimal nuclear atypia Excessive vascular proliferation Abundant red blood cells RBC and hemosiderin extravasation Abundant lymphocytes and monocytes Premonitory sign Intracytoplasmic PAS +ve hyaline globules	Kaposi's sarcoma is commonly associated with acquired immune deficiency syndrome (AIDS)
Merkel cell carcinoma		Intracutaneous nodule	Shiny Flesh-colored or bluish-red	Firm	< 1 cm	Sun-exposed areas Head and neck Upper limbs and shoulder Lower limbs and hip Trunk	Milky red areas Linear Irregular vessels Polymorphous vessels	Uniform cells with large basophilic nuclei Single-cell necrosis Frequent mitoses Lymphovascular invasion Perineural invasion Epidermal involvement via pagetoid spread	Older individuals with light skin tones Rapidly growing
Basal cell carcinoma	Nodular basal cell carcinoma	Papule	Flesh-colored	Small bump	Variable	Face	Focused, bright red, and branching arborizing vessels Loosely arranged blue-gray dots	Nest-like infiltration with basaloid cells	May have a "rolled" border
	Superficial basal cell carcinoma	Patch	Erythematous	Scaly	1 to > 10 cm	Sun-exposed areas Head (cheek and nose) Trunk	Superficial fine telangiectasia Shiny white to red, translucent or opaque structureless areas Multiple small erosions	Large, hyperchromatic, oval nuclei Minimal cytoplasm Small basaloid nodules	Higher incidence in men
	Sclerosing basal cell carcinoma (morpheaform)	Papule Plaque	Flesh-colored Slightly erythematous	Firm Indurated Indistinct borders	Variable	Sun-exposed areas	Whitish background Few fine arborizing vessels Multiple brown dots Ulceration	Thin columns + small nodules Highly collagenized stroma	Expression of smooth muscle protein alpha-actin in tumor stroma
Prurigo nodules		Dome-shaped nodule	Flesh-colored Erythematous Brown/black	Firm	Variable	Extensor surfaces of the arms and legs and on the trunk Upper back, abdomen, and sacrum	White "starburst pattern" surrounding red/brown/yellow crusts Erosions Hyperkeratosis	Thick and compact orthohyperkeratosis Irregular epidermal hyperplasia Focal parakeratosis with irregular acanthosis Nonspecific dermal infiltrate containing WBCs	Nodules range in number from few to hundreds Worsened by heat, sweating, or irritation from clothing
Melanoma	Melanoma in situ (Lentigo Maligna)	Macule	Variable (from light to dark brown, black, pink, red, or white)	Smooth	Around 1 cm	Sun-damaged skin of the head or neck	Asymmetric, pigmented follicular openings Gray angulated lines Gray areas, dots, and globules Circle within a circle	↑ atypical spindle shaped melanocytes Arranged in single cells or in small nests along the dermal-epidermal junction	Darkening of pigmentation, sharpening of borders, or emergence of nodular areas are signs of progression to lentigo maligna melanoma
	Lentigo maligna melanoma	Macule	Brown/tan	Freckle-like	Variable	Chronically sun-damaged areas	Asymmetric, pigmented follicular openings Gray angulated lines Gray areas, dots, and globules Circle within a circle	"Star-burst giant cells" in epidermis "Swallow's nest" sign along the dermal-epidermal junction Minimal cytoplasm Pale nucleus with small nucleoli	Usually in older individuals
	Superficial spreading melanoma	Macule Plaque with irregular borders	Variably pigmented (red, blue, black, gray, and white)	Thin	1 mm to > 1 cm	Anywhere but usually: Back (men and women) Lower extremities (women)	Asymmetry of shape > 2 colors Asymmetry of structures	Asymmetric Poorly circumscribed Lack cellular maturation	Lateral (radial) growth before vertical (invasive) growth
	Nodular melanoma	Polypoid nodule	Dark color	Lump	6mm to > 1 cm	Trunk Head Neck	Pigment network or pseudonetwork Aggregated brown or black globules Blue pigmentation within lesion Small dotted or comma vessels	Cells proliferate downwards through the skin Dermal growth in isolation or in association with an epidermal component	Two-thirds arise in normal skin, the rest in existing moles Rapidly enlarging
	Acral lentiginous melanoma	Macule Patch	Dark brown to black	Raised areas Ulceration Bleeding	Variable	Palmar Plantar Subungual Mucosal surfaces	Parallel-ridge pattern Irregular diffuse pigmentation	Asymmetric proliferation of single melanocytes at dermoepidermal junction	Most common among dark skinned individuals
	Amelanotic melanoma	Patch	Skin color	Slightly elevated borders	Around 6 mm	Sun-exposed areas	No melanin pigmentation Dotted vessels Linear irregular vessels		Lesions not pigmented since they don't produce melanin
Common nevus		Dome-shaped nodules	Hypopigmented	Smooth surface Terminal hairs often present	1 cm to > 20 cm	Sun-exposed areas above the waist	Comma-shaped or curved vessels Structureless light brown background Residual brown thick circles around the hair follicles	Multinucleated melanocytes Melanocytes diffusely infiltrate dermis	Also called Miescher nevus
Blue nevus		Macule Papule	Blue	Smooth	Variable	Head and neck, Dorsal aspect of the distal extremities Sacral area	Structureless blue pigmentation Structureless blue and white or blue and brown on some occasions	Proliferation of dendritic, dermal, melanin-producing melanocytes	Also called Mongolian spots
Spitz nevus	Nonpigmented Spitz nevus	Nodule	Pink	Smooth	< 1 cm	Cheek	Coiled vessels White network over a pink to reddish background		In children and adolescents
	Reed-like Spitz	Papule	Heavily pigmented	Smooth	< 1 cm	Head and neck Upper and lower extremities	Structureless black to gray center Hypopigmented follicular openings Peripheral streaks Pseudopods Globules	Enlarged spindle melanocytes with polyangular form "Ground glass" cytoplasm	Most commonly develops in children, adolescents, and young adults.
Solar lentigo		Multiple spots	Brown	Smooth	Around 5mm	Sun-exposed areas	Faint pigmented fingerprint structures Structureless pattern Light brown pseudonetwork with well-defined borders and a "moth-eaten" edge	↑ melanin deposition in keratinocytes ↑ linear arrangement of melanocytes at the dermal-epidermal junction	Associated with UV exposure and skin aging
Sebaceous hyperplasia		Papule	Skin-colored to brownish	Umbilicated	2 - 6 mm	Forehead Nose Cheeks	Structureless yellow to whitish center surrounded by short linear "crown vessels"		Usually in middle-aged or older patients
Lichen planus-like keratosis		Papule Plaque	Gray to brown	Prominent	Variable	Upper trunk	Shows a coarse or fine, gray to blue, granular pigmentation Diffuse brownish gray granules	Hypergranulosis Epidermal hyperplasia Superficial bandlike infiltrate Melanophages	Appearance depends on stage of evolution