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Background

Nowhere in pathology is the accurate correlation between the clinical appearance of a patient's lesions and the histologic appearance of the microscopic slide more important than the diagnosis of skin rashes.  Many skin rashes have similar histologic appearances, in spite of the very different clinical appearance on the patient.  Conversely, similar clinical lesions may have vastly different histologic appearances. 

Acanthosis nigricans
Acne Rosacea
Acne Vulgaris
Acral Pseudolymphomatous Angiokeratoma of Children (APACHE)
Acral persistent papular mucinosis
Acrodermatitis Enteropathica
Acute Generalized Exanthematous Pustulosis (AGEP)
Alopecia mucinosa (Follicular mucinosis)
Angiolymphoid Hyperplasia with Eosinophilia
Anti-p200 Pemphigoid
Anti-p450 Pemphigoid
Argyria
Arthropod Bites (Bug Bite)
Atopic Dermatitis
Autoimmune Progesterone Dermatitis
Axillary Granular Parakeratosis
Benign Cephalic Histiocytosis
Brachioradial Pruritis
Bullous pemphigoid
Calciphylaxis
Cellulitis
Chilblains
Cholesterol Emboli Syndrome
Chondrodermatitis Nodularis Helicis
Chronic Papillomatous Dermatitis
Cicatricial pemphigoid
Clear Cell Papulosis
Contact Dermatitis
Cryoglobulinemia
Cutaneous mucinosis of infancy
Cutaneous myxoma
Darier's Disease (Keratosis follicularis)
Deep lamina lucida pemphigoid (Anti-p105kd bullous dermatosis)
Degos Disease (Malignant Atrophic Papulosis)
Dermal disorders (Disorders of collagen, elastic fibers, mucin, scar, cicatrix)
Dermal mucinosis
Dermatitis herpetiformis
Dermatomyositis
Dermatophyte (Tinea, Ringworm)
Digital mucous cyst
Drug Reactions
Eczema
Eosinophilic Fasciitis
Eosinophilic Folliculitis (Ofuji's Disease)
Epidermolysis Bullosa
Epidermolysis bullosa acquisita
Erosive Pustular Dermatosis
Erythema annulare centrifugum (Gyrate erythema)
Erythema Elevatum Diutinum
Erythema Induratum (Nodular Vasculitis)
Erythema multiforme
Erythrasma
Erythroderma
Erythromelanosis follicularis et colli
Favre-Racouchot Disease (Nodular Elastosis with Cysts and Comedones)
Fibroblastic Rheumatism
Fixed drug eruption
Flegel's Disease (Hyperkeratosis Lenticularis Perstans)
Focal mucinosis
Gangrene
Gianotti-Crosti Syndrome
Graft-versus-host disease
Granuloma annulare
Granuloma faciale
Granulomatous Periorificial Dermatitis
Grover's Disease (Transient Acantholytic Dyskeratosis)
Hailey-Hailey Disease (Benign Familial Pemphigus)
Hand Foot Mouth Disease
Herpes gestationis (Pemphigoid gestationis)
Hidradenitis Suppurativa
Histiocytoses
Hydroa Vacciniforme
Hyper IgD Syndrome
Hyper IgE Syndrome
Ichthyosis
Incontinentia pigmenti
Interstitial Granulomatous Dermatitis
Jessner's Lymphocytic Infiltrate of the Skin
Kawasaki's syndrome
Kimura's Disease
Langerhans Cell Histiocytosis
Lichen nitidus
Lichen planus
Lichen planus-like keratosis
Lichen sclerosis et atrophicus (LSEA)
Lichen striatus
Lichenoid Dermatoses and tissue reactions
Linear IgA disease
Lupus erythematosus (SLE, DLE, SCLE)
Lymphomatoid Papulosis (LyP)
Morphea
Mucocele
Mucopolysaccharidoses
Myxedema, Generalized
Myxedema, Pretibial
Necrobiosis lipoidica
Necrobiotic xanthogranuloma
Necrolytic Migratory Erythema
Necrotizing Fasciitis
Neonatal Cephalic Pustulosis
Nephrogenic Fibrosing Dermopathy
Neutrophilic Eccrine Hidradenitis
Nevus mucinosis
Onychomycosis
Palmoplantar Hidradenitis (Idiopathic)
Papular mucinosis (Lichen myxedematosus)
Paraneoplastic Pemphigus
Pemphigus erythematosus
Pemphigus foliaceus
Pemphigus vegetans
Pemphigus vulgaris
Perniosis
Photosensitive Disorders
Pigmented Purpuric Dermatoses
Pityriasis Lichenoides et Varioliformis Acuta (PLEVA, Mucha-Habermann Disease)
Pityriasis Lichenoides Chronica
Pityriasis Rosea
Pityriasis Rubra Pilaris
Poikilodermas
Polymorphous Light Eruption
Porokeratosis
Porphyria
Prurigo Pigmentosa
Pseudoporphyria
Psoriasis
Pustular Psoriasis
Pyoderma gangrenosum
Reactive angioendotheliomatosis
Reticular erythematous mucinosis
Rosacea
Scleredema
Scleroderma
Scleromyxedema
Scurvy
Shingles (Herpes Zoster)
Sneddon-Wilkinson Dermatosis (Subcornal Pustular Dermatosis)
Sweet's Syndrome (Acute Febrile Neutrophilic Dermatosis)
Tinea versicolor (Pityriasis versicolor)
Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
Urticaria
Vasculitis
Xanthoma

OUTLINE

Histopathological Features and Variants
Differential Diagnosis
Commonly Used Terms
Internet Links

HISTOPATHOLOGICAL VARIANTS	CHARACTERIZATION
HYPERSENSITIVITY REACTION
The clinical and histopathologic spectrum of "dermal hypersensitivity reactions," a nonspecific histologic diagnosis that is not very useful in clinical practice, and the concept of a "dermal hypersensitivity reaction pattern". Fung MA. Department of Dermatology, University of Connecticut School of Medicine.	J Am Acad Dermatol 2002 Dec;47(6):898-907 Abstract quote BACKGROUND: "Dermal hypersensitivity reaction" (DHR) is diagnosed by dermatopathologists but is not an accepted clinical disease entity. There are no clear guidelines for its diagnosis, differential diagnosis, or management. OBJECTIVES: The objectives were to define the histologic criteria for cases histologically diagnosed as DHR and identify corresponding clinical disorders. METHODS: Skin biopsy specimens from 130 patients diagnosed as "consistent with DHR" were reviewed. Additional information was obtained from patients, their dermatologists, and medical records. RESULTS: Follow-up in 74 of 110 patients (median, 26.6 mo) revealed, most commonly, diagnoses of urticaria, drug reactions, and spongiotic (eczematous) dermatitis. Among the remaining cases, 37 of 59 reported persistence of disease, some exhibiting a uniform phenotype characterized by excoriated, edematous papules on the trunk. Histopathologic features present in more than 90% of 143 biopsy specimens included superficial and mid-perivascular lymphocytic infiltrates with eosinophils. CONCLUSION: DHR is a perivascular lymphocytic dermatitis with eosinophils involving the papillary and upper reticular dermis and minimal, if any, primary epidermal alteration. The term DHR does not represent any known clinical disorder; rather, it corresponds to many clinical disorders. The use of the phrase "dermal hypersensitivity reaction pattern" may be helpful in conveying the idea that a particular histologic pattern may be seen in a number of clinical disorders.
PRETIBIAL PRURITIC PAPULAR DERMATITIS
Pretibial Pruritic Papular Dermatitis: A Distinctive Cutaneous Manifestation in Response to Chronic Rubbing. Annessi G, Petresca M, Petresca A. Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.	Am J Dermatopathol. 2006 Apr;28(2):117-121. Abstract quote   We describe the clinico-pathologic features of 44 patients with a peculiar pretibial pruritic papular dermatitis (PPPD). Clinically, PPPD consists of discrete, roundish, extremely pruritic papules with a smooth surface caused by the delicate and persistent rubbing of pretibial skin. Histologically, PPPD showed minimal compact orthokeratosis, flattening of the rete ridges, a superficial and mid-dermal perivascular and interstitial infiltrate of lymphocytes, histiocytes, eosinophils and multinucleated fibroblasts, and thickened collagen bundles in haphazard array in the superficial dermis. The clinical picture of PPPD closely resembled that of lichen simplex chronicus/circumscribed neurodermatitis or lichen amyloidosus. Histologically, the absence of uneven psoriasiform epidermal hyperplasia, marked compact orthokeratosis, hypergranulosis, and coarse bundles of collagen arranged in vertical streaks in the papillary dermis distinguished PPPD from lichen simplex chronicus, whereas the lack of amyloid deposits in the dermal papillae differentiated PPPD from lichen amyloidosus. We suggest that PPPD is an unusual morphologic expression of gentle and chronic rubbing of pretibial skin with distinctive histopathologic features.
SOFT TISSUE FILLERS
Adverse cutaneous reactions to soft tissue fillers--a review of the histological features. Dadzie OE, Mahalingam M, Parada M, El Helou T, Philips T, Bhawan J. Department of Dermatopathology and Section and Department of Dermatology, Boston University Medical Center, Boston, MA 02118, USA.	J Cutan Pathol. 2008 Jun;35(6):536-48. Abstract quote The enhanced use of exogenous substances for cosmetic and reconstructive procedures is paralleled by an increase in reports of cutaneous adverse reactions to several of these agents. Recognition of the histological features of these reactions is of importance to both dermatologists and dermatopathologists but is not always easy for several reasons. First, cost-related issues are resulting in an increasing number of these procedures being performed overseas. Thus, patients are often unsure about the exact product used. Compounding this is the fact that practitioners who perform these procedures are not forthright in divulging this information, given that improper substances may be admixed in the filler injected. Furthermore, cutaneous reactions may occur at sites distant from injected sites, secondary to migration of the filler substance and a lapse of months to years may occur prior to the development of a cutaneous reaction. Thus, a causal relationship between the procedure and the reaction is often not made. We present an overview of the histological features of adverse reactions to currently available soft tissue fillers, both in the United States and overseas, in an attempt to enhance awareness of the diversity of these reactions.

Cicatrix-Scar.

Diffuse/Nodular Dermatitis

Dermal Histologic Pattern	Diagnosis
Lymphocytes	Pseudolymphoma Lymphoma
Neutrophils	Sweet's syndrome Inflammatory bowel disease Rheumatoid neutrophilic dermatitis Pyoderma gangrenosum Follicular cyst, ruptured Granuloma faciale Erythema elevatum diutinum
Neutrophils and eosinophils	Granuloma faciale Erythema elevatum diutinum
Plasma cells	Rhinoscleroma Leishmaniasis Syphilis, primary Chancroid Granuloma inguinale Lymphogranuloma venereum Pseudolymphoma Granuloma faciale Erythema elevatum diutinum
Mast cells	Urticaria pigmentosa, nodular
Abnormal leukocytes	Extramedullary hematopoisis Pseudolymphoma Lymphoma
Histiocytes	Botryomycosis Blastomycosis-like pyoderma Rhinoscleroma Actinomycosis Nocardiosis Streptomycosis Cryptoococcosis Histoplasmosis Blastomycosis Paracoccidioidomycosis Chromomycosis Coccidioidomycosis Sporotrichosis Rhinosporidiosis Kerion Candida granuloma Eumycetoma Phycomycosis Alternariosis Dermatophytosis (Majocchi's granuloma) Protothecosis Amebiasis Acne congobata/acne keloidalis Hidradenitis suppurativa Dissecting cellulitis of the scalp Pilondial sinus Follicular cyst, ruptured Halogenoderma Tuberculosis cutis verrucosa Atypical mycobaterial infections Leprosy Dermatofibroma, early Langerhans' cell histiocytosis Granulomatous slack skin
Histiocytes and Lipophages	Xanthelasma Xanthoma Xanthoma disseminatum Verruciform xanthoma Xanthogranuloma Generalized eruptive histiocytoma Malacoplakia Silicone granuloma Paraffinoma

Interface Dermatitis

Interstitial-Refers to the location of inflammatory cells between vessels within the dermis. 

Lichenoid-Epidermal basal cell damage with vacuolar degenerative changes associated with inflammatory cells.

Panniculitis-Inflammation of the fat.

Spongiosis-Refers to edema or swelling between the epithelial cells.  It is the histologic correlation of eczema.

Subepidermal Vesicular Dermatitis

Dermal Histologic Pattern	Diagnosis
Little or no infiltrate	Epidermolysis bullosa, junctional, dermolytic, acquired Bart syndrome Hypoxemia plus pressure Acute burn Erythema multiforme, severe
Lymphocytes	Erythema multiforme LSEA Mucha-Habermann disease Lichen planus, bullous Pseudolymphoma Lymphoma
Eosinophils	Bullous pemphigoid Herpes gestationis Acquired EB Arthropod
Neutrophils	Dermatitis herpetiformis DH-like drug eruption Linear IgA disease EBA SLE Leukocytoclastic vasculitis Septic vasculitis Pyoderma gangrenosum Cellulitis Bullous pemphigoid Herpes gestationis Cicatricial pemphigoid
Eosinophils and neutrophils	Dermatitis herpetiformis DH-like drug eruption Linear IgA disease EBA Bullous pemphigoid Herpes gestationis
Mast Cells	Urticaria pigmentosa

Superficial Perivascular Dermatitis-Refers to the location of inflammatory cells around the superficial portions of the dermal blood vessels.

Epidermal Changes	Dermal Histologic Pattern	Diagnosis
No epidermal changes
	Superficial Perivascular Dermatitis
	Lymphocytes predominate	Tinea versicolor Dermatophytosis Erythrasma Pitted keratolysis Vitiligo Schamberg's disease Viral exanthems Drug eruption (one type) Urticaria, late Erythema figuratum, superficial
	Superficial perivascular and interstitial dermatitis
	Lymphocytes predominate	Schamberg's disease Pruritic urticarial papules and plaques of pregnancy (PUPPP)
	Neutrophils predominate	Dermatitis herpetiformis Linear IgA dermatosis Dermatitis herpetiformis-like drug eruptions Acute discoid lupus erythematosus/SLE Leukocytoclastic vasculitis Erythema marginatum
	Eosinophils predominate	Bullous pemphigoid/Herpes gestationis, urticarial Pemphigus vulgaris, urticarial Arthropod PUPPP
	Neutrophils and eosinophils predominate	Urticaria
	Melanophages predominate	Postinflammatory pigmentary alteration Macular amyloidosis
	Siderophages predominate	Stasis
	Macrophages with features of melanophages and siderophages predominate	Minocycline-induced eruption
	Mast cells predominate	Urticaria pigmentosa Brachioradial pruritis
Ballooning changes	Lymphocytes predominate-ballooning mostly	Herpesvirus infection
	Lymphocytes predominate	Measles
	Psoriasiform and lymphocytes predominate	Orf Milker's nodule
Spongiosis
	Lymphocytes predominate	Allergic contact dermatitis Nummular dermatitis Dyshidrotic dermatitis Id reaction Photoallergic dermatitis, early Dermatophytosis Miliaria rubra Gianotti-Crosti syndrome Pityriasis rosea Erythema annulare centrifugum Seborrheic dermatitis Lichen striatus Pityriasis alba Mycosis fungoides, macule/patch
	Eosinophils predominate	PUPPP Allergic contact dermatitis Nummular dermatitis Dyshidrotic dermatitis Id reaction Bullous pemphigoid Herpes gestationis Pemphigus vulgaris, urticarial Incontinentia pigmenti Toxic erythema of newborn Arthropod assault
Spongiotic Psoriasiform	Lymphocytes predominate	Allergic contact dermatitis Nummular dermatitis Dyshidrotic dermatitis Id reaction Seborrheic dermatitis Nonbullous congenital ichthyosiform erythroderma Lichen striatus
Spongiotic Lichenoid	Lymphocytes predominate	Lichen striatus Bullous pemphigoid Herpes gestationis, urticarial
		Mycosis fungoides
Spongiotic Psoriasiform Lichenoid	Lymphocytes predominate	Lichen striatus Bullous pemphigoid Herpes gestationis, urticarial Mycosis fungoides
Psoriasiform only
	Lymphocytes predominate	Psoriasis Allergic contact dermatitis Nummular dermatitis Dyshidrotic dermatitis Pityriasis rubra pilaris Seborrheic dermatitis Dermatophytosis Candidiasis Lichen simplex chronicus Prurigo nodularis Acanthoma fissuratum Pressure papule from prosthesis Surfer's nodules Chondrodermatitis nodularis helicis
Psoriasiform Lichenoid	Lymphocytes predominate	Lichen striatus Mycosis fungoides Inflammatory linear verrucous epidermal nevus
	Histiocytes and plasma cells predominate	Syphillis, secondary

Superficial and Deep-Refers to the location of inflammatory cells around the superficial or deeper portions of the dermal blood vessels.

Epidermal Changes	Dermal Histologic Pattern	Diagnosis
No epidermal changes
	Perivascular Dermatitis
	Lymphocytes predominate	Polymorphous light eruption, early Erythema figuratum Erythema chronicum migrans Pernio Erythema nodosum PMLE DLE, tumid CLL B-cell lymphoma
	Eosinophils prominent	Arthropod insult
	Plasma cells prominent	Erythema chronicum migrans Scleroderma
	Histiocytes and lymphocytes prominent	Leprosy, indeterminate
	Perivascular and Interstitial Dermatitis
	Neutrophils	Suppurative folliculitis, periphery Neutrophilic eccrine hidradenitis Flea bite Cellulitis Erythropoietic protoporphyria
	Eosinophils	Arthropod Erythema chronicum migrans Well's syndrome
	Eosinophils and neutrophils	Urticaria
	Plasma cells	Erythema chronicum migrans
	Neutrophils, eosinophils, plasma cells	Scleroderma, early
	Histiocytes predominate	Granuloma annulare Necrobiosis lipoidica Interstitial granulomatous dermatitis with arthritis Mycosis fungoides, granulomatous
Ballooning Epidermal Changes
	Lymphocytes predominate
	Ballooning only	Hyroa aestivale/Hydroa vacciniforme
	Interface	Herpesvirus Fixed drug eruption
	Spongiosis	Toxic shock syndrome
Spongiotic
	Lymphocytes	Photoallergic dermatitis Early PMLE
	Eosinophils	Arthropod Bullous pemphigoid Herpes gestationis, urticarial
	Psoriasiform lymphocytes	Photoallergic dermatitis Mycosis fungoides, plaque
	Lichenoid lymphocytes	Fixed drug eruption Dermatophytosis Acrodermatitis chronica atrophicans Mycosis fungoides, plaque
	Psoriasiform lichenoid lymphocytes	Mycosis fungoides, plaque
Psoriasiform
	Psoriasiform lymphocytes	Dermatophytosis Norwegian scabies Persistent light eruption Actinic reticuloid Pityriasis rosea, herald patch
	Lichenoid lymphocytes	Lichen striatus Mycosis fungoides, plaque
	Lichenoid histiocytes, plasma cells	Syphilis, secondary

Adopted from Algorithms go tHistologic Diagnosis of Inflammatory Skin Diseases. Third Edition. Ardor Scribendi 2005.
Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008

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Last Updated June 19, 2008

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