Atlas of Essential Dermatopathology-Springer London (2013)

Atlas of Essential Dermatopathology
Kasia S. Masterpol • Andrea Primiani

Lyn M. Duncan
Atlas of Essential
Dermatopathology
Kasia S. Masterpol, MD Lyn M. Duncan, MD
Boston Medical Center Massachusetts General Hospital
Department of Dermatology WRN825, Dermatopathology Unit
Boston, MA Boston, MA
USA USA
Andrea Primiani, MD
Massachusetts General Hospital
WRN2, Pathology Service
Boston, MA
USA
ISBN 978-1-4471-4470-0 ISBN 978-1-4471-4471-7 (eBook)

DOI 10.1007/978-1-4471-4471-7
Springer London Heidelberg New York Dordrecht
Library of Congress Control Number: 2012954534
© Springer-Verlag London 2013

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Preface
Atlas of Essential Dermatopathology is based on a sketchbook developed during

Dermatopathology teaching signout at the Massachusetts General Hospital. While reviewing
cases at the microscope, Dr. Duncan draws sketches to outline key diagnostic features. Many
years ago she created a sketchbook that contained these teaching templates. As the years have
progressed many trainees have made copies of the book. Dr. Szyfelbein Masterpol and Dr.
Primiani provided the enthusiasm, motivation and ground work required to move this work
from a book of hand drawn sketches and tables to a color atlas with outlines and histological
images.
The content is based on the most frequently encountered processes in the MGH
Dermatopathology Unit; it is not intended to be comprehensive but rather an outline and atlas
of the essentials in diagnostic Dermatopathology. Each chapter is brief, a couple of pages, they
are vignettes (literally something that would fit on a vine leaf), and focus on the main points.
Tables of special stains, immunohistochemical markers and a glossary of terms are also
included.
The goal of the book is to be a primer for trainees of all levels – students and residents alike – in
dermatology and pathology.
Boston, MA, USA Kasia S. Masterpol, MD

Andrea Primiani, MD
Lyn M. Duncan, MD
v
Acknowledgements
Thank you to Rosalynn M. Nazarian, M.D., for her help in creating the chart on immunohis-
tochemistry of epithelial proliferations and Irwin Roth, M.D., for the image of the brown
recluse spider.
vii
Contents
Part I Anatomy
1 Basic Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2 Adnexal Anatomy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
3 Nail Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Part II Infections
4 Parasites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
5 Verruca Vulgaris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
6 Herpes Simplex Virus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
7 Superficial Fungal Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
8 Aspergillosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
9 Deep Fungal Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Part III Inflammatory, Non-Infectious
10 Epidermolysis Bullosa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
11 Acantholytic Processes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
12 Autoimmune Blistering Dermatoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
13 Porokeratosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
14 Interface Dermatitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
15 Lichenoid Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
16 Psoriasiform Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
17 Perforating Dermatoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
18 Non-infectious Palisading Granulomatous Dermatitis. . . . . . . . . . . . . . . . . . . . 40
19 The Seven L’s of Superficial and Deep Perivascular
Mononuclear/Lymphoid Infiltrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
20 Vasculitis and Vasculopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Part IV Nodular Lymphoid Proliferations
21 Lymphoid Antigens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
22 Lymphoid Follicles in Hyperplasia and Neoplasia . . . . . . . . . . . . . . . . . . . . . . . 50
ix
x Contents
Part V Epithelial Proliferations
23 Immunohistochemistry of Epithelial Proliferations . . . . . . . . . . . . . . . . . . . . . . 54

24 Actinic Keratosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
25 Progression of Actinic Keratosis to Squamous Cell Carcinoma . . . . . . . . . . . . 58
26 Vulvar Dysplasia and Neoplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
27 Nested Intraepidermal Proliferations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
28 Clinical Differential Diagnosis of Histological Squamous
Cell Carcinoma In-Situ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
29 Basal Cell Carcinoma (BCC) Types . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
Part VI Adnexal Tumors
30 Sebaceous Neoplasms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
31 Nevus Sebaceus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
32 Eccrine and Apocrine Neoplasms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
Part VII Mesenchymal Tumors
33 Immunophenotype of Dermal Spindled Cell Tumors. . . . . . . . . . . . . . . . . . . . . 78

34 Fibrous Papule (Angiofibroma) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
35 Angiokeratoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
Part VIII Melanocytic Proliferations
36 Lentigo versus Lentiginous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

37 Dermal Dendritic Melanocytic Proliferations . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
38 Dysplastic Nevi Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
39 Dysplastic Nevi Melanocytic Grading Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . 92
40 Congenital Melanocytic Nevi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
41 Types of Combined Nevi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
42 Benign Melanocytic Proliferations with Pagetoid Spread . . . . . . . . . . . . . . . . . 98
Part IX Reporting Melanoma
43 Invasive Primary Cutaneous Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102

44 Measuring Melanoma Thickness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
45 Melanoma Regression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
46 Counting Melanoma Mitoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
47 Reporting Tumor Infiltrating Lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
48 Lentigo Maligna, Lentigo Maligna Melanoma In Situ
and Lentigo Maligna Melanoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
Contents xi
Part X Special Stains
49 Histochemical Stains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116

50 Immunohistochemical Stains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Part I
Anatomy
1 Basic Anatomy
Epidermis Dermis
• Stratified squamous epithelium composed of layers of • Papillary dermis:
keratinocytes – Dermal papillae complement rete ridges of epidermis
– From superficial to deep: – Fine, pale eosinophilic collagen fibers
• Stratum corneum – Contains free nerve endings and Meissner’s corpuscles
• Stratum granulosum – Separated from the reticular dermis by the superficial
• Stratum spinosum vascular plexus
• Stratum basale • Reticular dermis:
• Intermingled cell types: – Thick, deeply eosinophilic collagen fibers
– Melanocytes: at dermoepidermal junction – Contains the deep vascular plexus, adnexal structures,
• Transfer melanin → keratinocytes nerve trunks, Pacinian corpuscles, glomus bodies
– Langerhans cells: CD1a + and Langerin + dendritic Subcutaneous Fat
cells in stratum spinosum • Separated into lobules by fibrous septae extending from
• Function in antigen presentation the reticular dermis
– Merkel cells: neuroendocrine cells in the stratum • Contains anagen hair bulbs and medium sized arterioles
basale, associated with nerve endings from the dermis and veins
2 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

DOI 10.1007/978-1-4471-4471-7_1, © Springer-Verlag London 2013
1 Basic Anatomy 3
Melanocyte
Langerhans Cell
Papillary Dermis
Superficial Vascular Plexus
Reticular Dermis
Subcutaneous Fat
Fig. 1.1 The skin is composed of epidermis (brown), dermis (pink) of the epidermis. The dermis is separated by the superficial vascular
and subcutaneous fat (yellow). Dendritic cells in the epidermis include plexus into the papillary dermis and reticular dermis
Langerhans cells in the stratum spinosum and melanocytes at the base
2 Adnexal Anatomy
Eccrine Unit – Phases: Anagen (growth), Catagen (involution), Telogen

• Eccrine Glands: palms, soles, forehead, axillae (resting phase)
– Coiled, secretory component in deep dermis – Hair shaft = composed of cuticle, cortex, and medulla
• Single layer of cuboidal epithelium, eosinophilic – Arrector pili = smooth muscle innervated by sympa-
cytoplasm thetic nervous system
• Surrounded by myoepithelial cells • Sebaceous Glands
• Eccrine Ducts – Acinar pattern, multiple lobules
– Long duct, extends from glandular coil in deep – Inner layers of cells with vacuolated, lipid-filled cytoplasm
dermis to exit through the epidermis as an – Outer rim of cuboidal basophilic germinative cells
acrosyringium – Short duct with stratified squamous epithelium, enters
– Two layers of epithelium, no myoepithelial cells into pilosebaceous unit
Pilosebaceous Apocrine Unit • Rarely the sebaceous duct exits through the epider-
• Hair Follicles mis directly
– Types: terminal (diameter ³0.06 mm), vellus (diameter • Apocrine Units: axillae, anogenital region, areola, eyelid
£0.03 mm) – Coiled, secretory component in dermis
– Zones (from superficial to deep): • “Decapitation secretion”, “snouts”
• Infundibulum = region above entry of sebaceous • Single layer of cuboidal to columnar epithelial cells,
gland duct eosinophilic cytoplasm
• Isthmus = extends from attachment of arrector pili • Surrounded by myoepithelial cells
muscle to entry of sebaceous gland duct – Short duct opens into infundibulum of associated hair
• Hair bulb = dermal papillae and hair matrix follicle

2 Adnexal Anatomy 5
Fig. 2.1 The cutaneous Hair Shaft

adnexal structures include the
pilosebaceous apocrine unit and
the eccrine unit. Apocrine
glands and sebaceous glands Acrosyringium
secrete their products into the
hair follicle through short ducts.
The sebaceous glands are often
seen in association with hair
follicles; apocrine glands are
more inconspicuous. The
smooth muscle arrector pili
connects the pilosebaceous
apparatus to the epidermis, Eccrine Duct
contraction of the arrector pili
ili
produces goose bumps. The
rP
eccrine unit is distinct and
cto
separate from the pilosebaceous
re
apocrine unit. The glands lay
Ar
deep in the dermis, coiled like a Sebaceous Eccrine Gland
garden hose, and are connected
to the epidermis by a long
Gland
straight eccrine duct. The coiled
exit of the eccrine duct through Eccrine Unit
the epidermis is termed the Pilosebaceous Apocrine Unit
acrosyringium
Fig. 2.2 Pilosebaceous Apocrine Unit. The sebaceous glands are asso- Fig. 2.3 Eccrine unit. The acrosyringium coils through the epidermis
ciated with hair follicles. Apocrine glands are lined by plump epithelial overlying the dermal eccrine duct. The glands are lined by secretory
cells with deep pink cytoplasm and surface blebs that are secreted by epithelium with pale pink cytoplasm; the ducts have less cytoplasm and
decapitation (inset) are more brightly pink (inset)
3 Nail Anatomy
Nail Nail root

• Dense keratinized plate • Base of the nail that underlies proximal nail fold
Nail bed Nail matrix
• Stratified squamous epithelium • Beneath the nail root
Eponychium • Germinative epithelium that produces the nail plate
• Distal edge of proximal nail fold

3 Nail Anatomy 7
Proximal Nail Fold
Nail
Basal Layer Squamous Epithelium

Nail Matrix Nail Bed
Proximal Nail Fold
Nail
Nail Matrix Pad

Nail Bed
Fig. 3.1 Sketch of the Nail Unit. The nail matrix is at the base of the nail plate beneath the proximal nail fold; distal to the nail matrix is the nail bed
Fig. 3.2 Nail matrix. The basaloid germinal epithelium of the nail Fig. 3.3 Nail bed. The nail bed epithelium forms the underside of the
matrix produces the nail plate (arrow); damage to the nail matrix will nail plate
lead to deformities of the nail plate
Part II
Infections
4 Parasites
Demodex Scabies
• Commonly seen in skin biopsies, especially those from • Mites, eggs, and larva found in burrows of stratum corneum
sebaceous areas • Superficial and deep perivascular eosinophilic inflammatory
• D. folliculorum – long and thin, aggregate in hair follicle infiltrate
infundibulum • Common in interdigital and flexural sites
• D. brevis – smaller, found singly in deeper sebaceous glands Spider Bites
• Common in hair follicles of the face • Dermal edema and hemorrhage
Tick Bites • Necrosis of blood vessel walls, thrombosis, and
• Chitinous body attached to skin, mouth parts embedded ulceration
in dermis • Variable superficial and deep perivascular lymphoid
• Dense superficial perivascular and interstitial mixed infiltrate with occasional eosinophils and neutrophils
inflammatory infiltrate, can extend deep into subcutis

4 Parasites 11
Fig. 4.1 Demodex. Located in the ostium of the hair follicle demodex Fig. 4.3 Scabetic mite. The mite Sarcoptes Scabiei burrows under the
mites are among the smallest of arthropods. These mites usually do not stratum corneum and causes intense itching
cause symptoms
Fig. 4.4 Brown recluse spider. Also known as the fiddleback spider,
Loxesceles reclusa range from 6 to 20 mm and have a characteristic
violin shaped marking on their dorsal cephalothorax (Image by Dr.
Irwin Roth)
Fig. 4.2 Tick. The chitinous body of the tick hovers over the epidermis
5 Verruca Vulgaris
Human Papilloma Virus (HPV) infection may lead to the for- • Columns of parakeratosis at rete peaks
mation of common warts (verruca vulgaris) • Hypergranulosis at valleys between rete ridges
Histologic Features: • Dermal papillae with dilated, ectatic capillaries
• Marked papillarity: acanthosis and elongation of rete ridges • Viral cytopathic changes with keratohyaline granule
• Intoeing of rete ridges at edges clumping (“koilocytes”) in upper epidermis

5 Verruca Vulgaris 13
Tiers of
Parakeratosis
Dilated Capillaries
Epidermis
Dermis
Valleys of Hypergranulosis
Fig. 5.1 Sketch of verruca vulgaris. The hyperkeratotic keratin forms tiers of parakeratosis alternating with valleys of keratinocytic hypergranulo-
sis. Dilated capillaries are present in papillary dermis
Fig. 5.2 Verruca vulgaris. A parakeratotic tier is present at the left of the image with underlying hypogranulosis. Hemorrhage is observed in the
superficial stratum corneum and prominence of the granular cell layer is present in the valleys between the rete ridges
6 Herpes Simplex Virus
• Epidermal intracytoplasmic edema, acantholysis, vesicle • Multinucleated cells with ground-glass nuclear inclu-
formation, and/or necrosis sions, nuclear molding, and margination of chromatin
– Acanthosis can be seen in chronic lesions – Cowdry bodies = eosinophilic nuclear inclusions composed
• Dermal lymphohistiocytic inflammatory infiltrate of nucleic acid and protein
• Follicular involvement and vasculitis can be seen • Type A = with surrounding halo, “owl-eye”
• Can detect viral particles by electron microscopy • Type B = fills nucleus
Fig. 6.1 Herpes Simplex. Epidermal keratinocytes infected with herpes virus display finely dispersed nuclear chromatin, nuclear inclusions and
multinucleate cells

6 Herpes Simplex Virus 15
Fig. 6.2 Sketch of viral

cytopathic effect of herpes virus
infection. Keratinocytes may
display bright pink intranuclear
inclusions, dispersion of nuclear Nuclear
chromatin with molding of the
nuclei to one another, and
Inclusions
multinucleate cells. The viral
particles have characteristic
capsid and surrounding envelope
Nuclear Multinucleated
Molding Cells
Viral Particles
by Electron Microscopy
7 Superficial Fungal Infections
Dermatophytes (Microsporum, Trichophyton, Pityrosporum ovale (Malassezia)

Epidermophyton) • Causes tinea versicolor or folliculitis
• Different clinical manifestations depending on the body • Histology:
site involved: – Short, stubby, unbranched hyphae and budding yeasts
– Tinea capitis, tinea corporis, tinea pedis, tinea unguium, in stratum corneum, “spaghetti and meatballs” = T.
tinea cruris, tinea barbae versicolor
• Histology: – Dilated hair follicle filled with basophilic keratina-
– Septate hyphae in stratum corneum (sandwiched ceous debris and spores in the dermis with inflammatory
between upper basket-weave layer and lower compact reaction = Pityrosporum folliculitis
ortho- or parakeratotic layer)
Candida
• Histology:
– Budding yeast and pseudohyphae

7 Super ficial Fungal Infections 17
Fig. 7.1 Onychomycosis. Delicate septate hyphae (dermatophyte) and Fig. 7.3 Tinea versicolor. Infection with Malassezia is not really a
budding yeast (candida) are present in the keratin, staining magenta “tinea”; the organism is not a dermatophyte. The yeasts admixed with
with periodic acid Schiff stain with diastase (PASD) delicate hyphae appear as “spaghetti and meatballs” in the stratum
corneum on PASD stain
Fig. 7.2 Tinea nigra. The phaeohyphomycosis Hortaea werneckii Fig. 7.4 Pityrosporum in follicular keratin. Pityrosporum are often
hyphae in the superficial stratum corneum have brown pigmentation on present in the hair follicle keratin as small basophilic yeasts
hematoxylin and eosin stain (H&E)
8 Aspergillosis
Aspergillus is a fungal organism that typically occurs in – Fungal organisms may be visible on H&E but are high-
immunocompromised patients. It has distinctive histomor- lighted by GMS and PAS-D stains
phology, with acute angle branching and hyphal septation. • Septate hyphae with acute angle branching
• Histology: • Fruiting bodies, “aspergillum”, are rarely seen in
– Vascular invasion and subsequent thrombosis are tissue
characteristic • The fruiting body of aspergillus resembles an asper-
– Often pauci-inflammatory if immunocompromised or gillum used to sprinkle holy water
may have granulomatous inflammation and abscess
formation

8 Aspergillosis 19
Fig. 8.1 Aspergillus. The

organisms in tissue sections
display acute angle branching
and vascular invasion
Fruiting Body
Hyphae with
Acute Angle
Branching
Aspergillum
Vascular Invasion
Fig. 8.2 Aspergillus on Gomori methenamine silver (GMS) stain with septate hyphae and branching at acute angles
9 Deep Fungal Infections
Zygomycoses (Rhizopus, Absidia, Mucor) Cryptococcosis

• Infection typically in immunosuppressed patients, includ- • Typically occurs in immunosuppressed patients
ing diabetics – Localized infection can occur in immunocompetent
• Thick, non-septate hyphae branch at right angles patients
Phaeohyphomycosis • Clusters of spores (3–8 mm) with clear capsule (5–10 mm),
• Typically in immunocompetent patients following trauma “soap bubbles”
or in immunosuppressed patients Blastomycosis (endemic in Mississippi and Ohio River
• Brown-black yeast and septate hyphae valleys and Southeastern U.S.)
– Seen in stratum corneum or within abscess in subcutis • Thick-walled, round, multinucleated yeasts (8–30 mm)
Chromomycosis with single broad-based bud
• Round, thick-walled, golden brown yeast forms (5–12 mm) Rhinosporidiosis
resembling “copper pennies” (sclerotic bodies, Medlar • Large, spherical sporangia (>300 mm) containing many
bodies) endospores (up to 7 mm)
Coccidioidomycosis (endemic in the southwestern United Lobomycosis (found in Central and South America)
States) • Thick-walled fungi (10 mm) arranged in chains
• Thick walled spherule (80–200 mm) with multiple
endospores (2–30 mm)
Paracoccidioidomycosis (endemic in South America)
• Thick walled yeast with multiple daughter cells attached
by narrow-based buds (6–60 mm), “captain’s wheel”
– Can be found intra- and/or extracellularly

9 Deep Fungal Infections 21
Chromomycosis
Phaeohyphomycosis
Mucormycosis
Cryptococcosis
Coccidioidomycosis Paracoccidioidomycosis
Blastomycosis Lobomycosis
Rhinosporidiosis
Fig. 9.1 The deep fungi that infect the skin have characteristic shapes and sizes
Part III
Inflammatory, Non-Infectious
10 Epidermolysis Bullosa
Epidermolysis bullosa encompasses a group of cutaneous phic based on the location of the cleavage plane. Electron
blistering disorders that are characterized by mechanical fra- microscopy or immunohistochemistry can help differentiate
gility of the skin. The inherited forms of epidermolysis the ultrastructural level at which a subepidermal blister
bullosa are designated either simplex, junctional or dystro- occurs.
Table 10.1 Subclassification of epidermolysis bullosa

Simplex Junctional Dystrophic Acquired
Level of blister formation Intraepidermal (suprabasal) Subepidermal Subepidermal Subepidermal
Ultrastructural site of blister formation Within basal keratinocyte Within lamina lucida Deep to lamina densa Deep to lamina densa
Targeted structure Intermediate filaments, Anchoring filament, Anchoring fibril Anchoring fibril
hemidesmosome hemidesmosome
Targeted proteins Keratin 5 and 14, plectin Laminin 5, a6b4 integrin Type VII collagen Type VII collagen
Pathogenesis Mutation Mutation Mutation Antibodies
Other Non-scarring Scarring
The location of the blister corresponds to the protein involved in the pathogenesis. Intraepidermal blisters are usually associated with erosions.
Subepidermal blisters may lead to ulceration, with basement membrane zone damage and scarring

10 Epidermolysis Bullosa 25
Epidermis
Hemidesmosomes
(intermediate filaments
connect to anchoring filaments
via plectin, α6β4 integrin)
Dermis
Basement membrane
Anchoring fibrils
(lamina lucida and lamina densa) (type VII collagen)
Fig. 10.1 Sketch of the structural elements of the epidermis and dermis affected in epidermolysis bullosa
Fig. 10.2 Dystrophic epidermolysis bullosa. A pauci-inflammatory Fig. 10.3 Junctional epidermolysis bullosa. Electron microscopy
subepidermal blister with underlying dermal fibrosis, suggestive of a reveals a split within the lamina lucida
scar
11 Acantholytic Processes
Acantholysis occurs in the epidermis when there is dissolu- basal layer of keratinocytes (suprabasal), full thickness, or in
tion or disruption of the intercellular attachments. The kera- the superficial epidermis. Some forms of acantholytic der-
tinocytes fall away from one another. Acantholysis may matosis result from an autoimmune reaction,
appear at any level of the epidermis: immediately above the immunofluorescence testing may be helpful.
Table 11.1 Differential diagnosis of acantholytic processes

Acantholytic Full thickness
dyskeratosis (corps acantholysis (dilapidated Suprabasal Verrucous epidermal
ronds and grains) brick wall) acantholysis hyperplasia Immuno-fluorescence
Darier’s disease (Keratosis + –
follicularis)
Hailey-Hailey disease + –
(Benign familial pemphigus)
Grover’s (TAD) + + + –
Pemphigus vulgaris + +
Chicken wire pattern, IgG
and C3, Ab to desmoglein 3
Pemphigus vegetans + + +
Chicken wire pattern, IgG
and C3, Ab to desmoglein 3
Warty dyskeratoma + + –
Neoplasia (AK, SCC) +/− +/− +/− +/− –
TAD transient acantholytic dermatosis, AK actinic keratosis, SCC squamous cell carcinoma

11 Acantholytic Processes 27
Fig. 11.1 Darier’s disease. There is intraepidermal acantholytic Fig. 11.3 Grover’s disease. Two patterns of acantholysis, full thickness
dyskeratosis, hyperkeratosis, and corps ronds and grains (inset) (center) and suprabasal (right)
Fig. 11.4 Pemphigus vulgaris. There is suprabasal acantholysis with

loss of the overlying epidermis
Fig. 11.2 Hailey-Hailey disease. There is intraepidermal acantholysis
throughout stratum spinosum resembling a dilapidated brick wall
12 Autoimmune Blistering Dermatoses
The autoimmune blistering dermatoses result from antibod- using reagents to detect antibodies deposited in a biopsy of
ies directed against proteins in the epidermis or superficial the patient’s skin.
dermis. Direct immunoflourescence testing is performed
Table 12.1 Differential diagnosis of autoimmune blistering dermatoses

Blister location Inflammatory infiltrate Immunofluorescence Pathogenesis
Pemphigus vulgaris Intraepidermal Eosinophilic spongiosis IgG and C3 on cell membranes, Antibodies to desmoglein 3
and mixed infiltrate “Chicken-Wire” (Desmosomes)
Paraneoplastic pemphigus Intraepidermal Mixed, can be lichenoid IgG and C3 on cell membranes and Associated with internal
linear at DEJ (Desmosomes and malignancies, (most commonly
hemidesmosomes) lymphoproliferative disorders)
Bullous pemphigoid Subepidermal Eosinophils and Linear IgG and C3 at DEJ Antibodies to BPAg1 and 2
Lymphocytes (Hemidesmosomes)
Bullous lupus Subepidermal Neutrophils IgG, C3, and IgA deposits at BMZ Antibodies to BMZ proteins
erythematous and in upper dermis (Colloid
bodies)
Dermatitis herpetiformis Subepidermal Neutrophils > Eosinophils Patchy granular deposits of IgA in Deposition of IgA in dermal
dermal papillae papillae
Linear IgA disease Subepidermal Neutrophils > Eosinophils Linear IgA at basement membrane Antibodies to basement
membrane proteins
Epidermolysis bullosa Subepidermal Minimal (if present, Linear IgG at basement membrane Antibodies to Type VII
acquisita mixed infiltrate) collagen
DEJ dermoepidermal junction, BMZ basement membrane zone

12 Autoimmune Blistering Dermatoses 29
Fig. 12.1 Bullous pemphigoid. There is a subepidermal blister with a Fig. 12.3 Dermatitis herpetiformis. Aggregates of neutrophils and
superficial dermal infiltrate of eosinophils and lymphocytes cellular debris are located intermittently along the tips of the papillary
dermal pegs
Fig. 12.2 Bullous pemphigoid. Direct immunofluorescence reveals a Fig. 12.4 Pemphigus vulgaris. Direct immunofluorescence reveals
linear deposition of C3 along the dermal epidermal junction intercellular deposition of IgG
13 Porokeratosis
Clinical features Histological features

There are several variants • Characterized by the presence of coronoid lamellae
• Porokeratosis of mibelli – a plaque that develops in – Column of parakeratosis, angled toward the center of
infancy or childhood the lesion, with a focal loss of the granular cell layer
• Disseminated superficial actinic porokeratosis (DSAP) – and dyskeratosis of the epidermal keratinocytes and
thin papules on the legs of older women (the most com- thinning of the epidermis beneath the column.
mon variant) • Center of the lesion can show atrophy with overlying
• Linear porokeratosis – follows the lines of Blaschko and hyperkeratosis and scattered dyskeratotic cells within the
occurs in infancy or childhood epidermis
• Punctate porokeratosis – tiny papules on the palms and • Lichenoid inflammatory infiltrate is often present
soles appear after adolescence. A variant is porokeratosis
palmaris et plantaris disseminata (PPPD) wherein lesions
appear at other body sites

13 Porokeratosis 31
Column of parakeratosis
Coronoid
Decreased granular
lamellae
cell layer
Epidermis
Dyskeratosis
Dermis
Coronoid lamella
Punch
biopsy
Fig. 13.1 The column of parakeratosis is usually angled toward the center of the lesion. It is important to biopsy the lesion at the margin in a
manner that includes the hyperkeratotic column and the underlying epidermis
Fig. 13.2 The parakeratotic column is flanked by attenuated stratum corneum on the left and normal basket-weave stratum corneum on the
right. The epidermis directly below the column has loss of the granular cell layer, dyskeratosis and epidermal thinning
14 Interface Dermatitis
Interface dermatitis is characterized by an inflammatory pro-

cess, often with vacuolar changes, occurring at the interface
of the epidermis and the dermis.
Table 14.1 The differential diagnosis of interface dermatitis

EM TEN DM LE GVHD PLC/PLEVA
Epidermal dyskeratosis, + + −/+ −/+ + −/+
satellite cell necrosis
Colloid, civatte, cytoid bodies + + + + + +
Epidermal atrophy +/− – + (Grotton’s papules + + –
have acanthosis)
Vacuolar interface changes +/− +/− +/− + + +
Epidermal lymphocyte + + – +/− + +
exocytosis
Full thickness epidermal – + – – – –
necrosis
Adnexal involvement – + – + + –
Follicular Follicular dyskeratosis, Follicular
dyskeratosis Periadnexal inflammation dyskeratosis
Deep perivascular – – – + – –
inflammation
Dermal eosinophils + + – – −/+ −/+
Other “Festooning” of Loss of rete ridges Interstitial mucin Erythrocyte
naked dermal papillae deposition extravasation
Satellite cell necrosis occurs when a dying keratinocyte is surrounded by lymphocytes. Colloid bodies are eosinophilic globules of cellular protein
that are present in the epidermis or superficial dermis. EM erythema multiforme, TEN toxic epidermal necrolysis, DM dermatomyositis, LE lupus
erythematous, GVHD graft versus host disease, PLC pityriasis lichenoides chronica, PLEVA pityriasis lichenoides et varioliformis acuta

14 Interface Dermatitis 33
Fig. 14.1 Toxic epidermal necrolysis. There is full thickness epider-

mal necrosis and detachment of the epidermis from the underlying
dermis Fig. 14.2 Dermatomyositis. There is epidermal atrophy, vacuolar
change at the dermal-epidermal junction and a sparse inflammatory
infiltrate
Fig. 14.3 Lupus erythematosus. Epidermal atrophy with follicular Fig. 14.4 Graft vs. Host disease. There is keratinocyte dyskeratosis
hyperkeratosis and an interface, perivascular and periadnexal and interface dermatitis
inflammatory infiltrate are observed
15 Lichenoid Dermatitis
Lichenoid dermatitis is characterized by a band like inflammatory infiltrate in the superficial dermis parallel to the epidermis.
In some cases the infiltrate abutts and obscures the dermal epidermal junction.
Table 15.1 Differential diagnosis of lichenoid dermatitis

Lichenoid drug Lichenoid
Lichen planus reaction Fixed drug eruption Lichen striatus Lichen nitidus keratosis Lichen sclerosus
Hyperkeratosis + + + + + + +
Parakeratosis – + −/+ + + + −/+
Focal Focal
Hypergranulosis + + – – – + +
Wedge shaped Wedge shaped
Acanthosis + + +/− +/− – +/− –
Irregular Irregular Atrophy
Cytoid bodies + + + + and dyskeratosis + + –
Lichenoid + + + −/+ + + +
infiltrate
Adnexal – – −/+ + – – –
involvement
Dermal – + −/+ – – −/+ –
eosinophils
Hyalinized cell – – – – – – +
poor dermis

15 Lichenoid Dermatitis 35
Fig. 15.1 Lichenoid dermatitis. There is wedge-shaped hypergranulo-

sis with irregular epidermal hyperplasia and a band of inflammation Fig. 15.3 Lichen sclerosus. There is eosinophilic homogenization of
along the epidermal base the subepidermal dermis with an underlying band of inflammation
Fig. 15.4 Fixed drug reaction. There is extensive epidermal dyskerato-

Fig. 15.2 Colloid bodies in lichen planus. The eosinophilic globules sis and interface dermatitis that may have a dense lichenoid
are extracellular and may be present in the epidermis or the superficial appearance
dermis, also known as Civatte bodies
16 Psoriasiform Dermatitis
Psoriasiform dermatitis is characterized by a hyperplasia of mis is relatively flat. The rete ridges are often attenuated at
the epidermis (acanthosis) that is regular, the rete are of the tips of the papillary dermis.
roughly equal size to one another and the base of the epider-
Table 16.1 Differential diagnosis of psoriasiform dermatitis

Lichen simplex chronicus/
Psoriasis prurigo nodularis Pityriasis rubra pilaris
Parakeratosis pattern Confluent Focal Checkerboard, “Notes on a scale” (alternating
ortho- and parakeratosis); Perifollicular
Hypogranulosis + – −/+
Hypergranulosis – + +/−
Superficial perivascular lymphocytes + + +
Papillary dermal fibrosis −/+ + −/+
Dermal eosinophils – + –
Other Intracorneal neutrophilic Nerve hyperplasia Dilated follicles with perifollicular parakeratosis
microabscesses

16 Psoriasiform Dermatitis 37
Fig. 16.1 Psoriasis. There is regular epidermal hyperplasia with Fig. 16.3 Psoriasis. Neutrophils are observed in the epidermis and as
attenuation of the epidermis at the tips of the papillary dermal pegs microabscesses in the stratum corneum
Fig. 16.4 Monro microabscesses. These collections of neutrophils in

Fig. 16.2 Psoriasis. Diffuse parakeratosis with loss of the underlying the stratum corneum are characteristic of psoriasis
epidermal granular cell layer is observed
17 Perforating Dermatoses
Reactive Perforating Collagenosis Kyrle’s Disease* (Hyperkeratosis Follicularis et

• Transepidermal elimination of deeply basophilic degener- Parafollicularis in Cutem Penetrans)
ate collagen fibers • Associated with chronic renal insufficiency and uremia
• Dermal chronic inflammatory infiltrate • Hyperkeratosis, acanthosis
• Trichrome positive • Epidermal invaginations with keratin and neutrophil-rich
Elastosis Perforans Serpiginosa debris-laden plug
• Epidermal intoeing with intraepidermal channel and • Transepidermal elimination of keratotic material
microabscesses • Absence of hair follicle or shaft fragments
• “Claw and ball”-like transepidermal elimination of elas- • Variable dermal lymphohistiocytic inflammatory
totic material, keratin, and basophilic inflammatory infiltrate
debris *Historically, Kyrle’s disease occurred in renal disease
• Elastic stain reveals thickened dermal elastic fibers abut- and displayed one or more of these patterns, because of
ting and exiting the epidermis significant overlap – there are no longer considered to be
• Variable granulomatous infiltrate distinct entities.
Perforating Folliculitis
• Hair follicle rupture with granulomatous dermal reaction
• Channel containing basophilic debris in follicle
epithelium

17 Perforating Dermatoses 39
Collagenosis
Elastosis
Perforans
Serpiginosa
Folliculitis
Fig. 17.1 The three patterns of perforating dermatoses include the extrusion of collagen through the epidermis, the entrapment of elastic fibers
within the epidermis and the perforation of dermal connective tissue elements into the hair follicle epithelium
18 Non-infectious Palisading
Granulomatous Dermatitis
There are many causes of granulomatous dermatitis, many are Sarcoidosis is included as an example of non-infectious
caused by infectious organisms. This chapter focuses on the granulomatous dermatitis that is rarely palisading.
three distinct types of non-infectious palisading dermatitis.
Table 18.1 Differential diagnosis of non-infectious palisading granulomatous dermatitis

Hypocellular central zone Multinucleate giant cells Neutrophilic debris Dermal location
Granuloma annulare (GA) Mucin (hyaluronic acid) +/− −/+ (+ when drug associated) S/M
Necrobiosis Lipoidica (Diabeticorum) Sclerotic collagen ++ – S/D
(NLD)
Rheumatoid nodule Zonal fibrin – ++ D/F
Sarcoid None ++ – S/M/D
S superficial, M mid-dermal, D deep dermal, F fat

18 Non-infectious Palisading Granulomatous Dermatitis 41
Fig. 18.1 Granuloma annulare. Lymphocytes and histiocytes palisade Fig. 18.3 Rheumatoid nodule. There is fibrinoid dermal necrosis with
around a hypocellular dermis with abundant basophilic mucin palisading zones of fibroblasts and inflammatory cells
Fig. 18.2 Necrobiosis lipoidica. Zones of eosinophilic sclerotic colla- Fig. 18.4 Sarcoidosis. Compact aggregates of epithelioid histiocytes
gen are observed with multinucleate giant cells may have a few lymphocytes at the periphery
19 The Seven L’s of Superficial and Deep
Perivascular Mononuclear/Lymphoid
Infiltrates
The mnemonic 7 L’s has been used to prompt the histological structures, particularly the eccrine units supports a diagnosis
differential diagnosis of a superficial and deep perivascular of lupus. The presence of eosinophils and reactive lymphoid
mononuclear and lymphoid infiltrate. The presence of prom- follicles may be seen in cutaneous lymphoid hyperplasia, par-
inent superficial dermal edema is seen in polymorphous light ticularly if the etiology is a persistent reaction to arthropod
eruption; whereas an infiltrate that involves the adnexal bite.
Table 19.1 The differential diagnosis of superficial and deep perivascular lymphoid infiltrates, epidermal and dermal changes
Periadnexal
Epidermal changes Dermis inflammation Lymphoid follicles Eosinophils
Lupus Atrophy, interface Mucin + – –
Lymphocytic infiltrate Atrophy, interface Mucin + – –
of Jessner
Polymorphous light Acanthosis, Edema – – –
eruption (PMLE) dyskeratosis
Lyme- Gyrate Borrelia None or puncture site – – – –/+
Lues (syphillis) Hyperplasia Plasma cells –/+ – –
Leukemia (rare) – – – – –
(CLL)
Lymphocytoma (CLH) – – – –/+ –/+
CLL chronic lymphocytic leukemia, CLH cutaneous lymphoid hyperplasia

19 The Seven L’s of Super ficial and Deep Perivascular Mononuclear/Lymphoid Infiltrates 43
Fig. 19.1 Polymorphous light eruption. There is prominent papillary dermal edema and epidermal acanthosis
Fig. 19.2 Erythema chronicum migrans (Lyme disease, gyrate erythema). There are minimal epidermal changes. A perivascular mononuclear
infiltrate with scattered eosinophils is present
20 Vasculitis and Vasculopathy
Vasculitis is characterized by damage to the vascular endothelium inflammation. Leukocytoclastic vasculitis is characterized
and necrosis of the vessel wall; vasculopathy demon- by the presence of neutrophils, nuclear dust (leukocytoclasia)
strates intravascular thrombosis often without significant and fibrinoid necrosis of vessel walls.
Table 20.1 Characteristics of vasculitis and vasculopathy

Purpura fulminans,
Mixed cryoglobulinemia, Monoclonal cryoglobulinemia, Lymphocytic
Protein C deficiency, DIC, Coumadin (Warfarin) vasculitis,
Sepsis, Lupus anticoagulant necrosis Drug-induced Bechet’s disease, Perniosis
Intraluminal vascular −/+ + +/− −/+
thrombi
Vascular wall necrosis + −/+ +/− +/−
Neutrophils, + – – −/+
leukocytoclasia
Eosinophils – – +/− −/+
Lymphocytes – – + +
DIC disseminated intravascular coagulopathy

20 Vasculitis and Vasculopathy 45
Fig. 20.1 Purpura fulminans. The superficial dermal vessels are Fig. 20.3 Henoch - Schoenlein purpura (HSP). There is a leukocytoclastic
occluded by microthrombi, there is minimal inflammation vasculitis, characterized by the presence of nuclear debris and fibrinoid
necrosis of the vessel wall
Fig. 20.2 Monoclonal cryoglobulinemia. The superficial dermal vessels Fig. 20.4 Perniosis. There is a lymphocytic vasculitis without
are occluded by homogeneous thrombi that may be clefted, there is significant neutrophilic infiltrate or intraluminal thrombi
minimal inflammatory infiltrate
Part IV
Nodular Lymphoid Proliferations
21 Lymphoid Antigens
Immunohistochemistry is a valuable tool in the analysis of developed to detect cellular proteins that characterize cells as
lymphocytic infiltrates. Specific antibody reagents have been to lineage and differentiation state.
Table 21.1 Lymphoid antigens commonly detected in the immunohistochemical analysis of cutaneous lymphoid infiltrates
Normal cells Tumors Uses
CD2 Most T cells CTCL May be lost in some CTCL
CD3 T cells CTCL Best Pan-T cell marker
CD4 T Helper cells Most MF Normal CD4:CD8 » 2:1
CD5 T cells, some B cells CLL, some pcMZL Occasional loss in CTCL,
co-expression with CD43
and CD20 = CLL or pcMZL
CD8 T Suppressor cells Aggressive epidermotropic CD8+ Normal CD4:CD8 » 2:1
CTCL; Indolent CD8+ lymphoid
proliferation of the ear
CD10 Follicle center cells FCL, some MZL Positive in FCL
CD20 B cells B cell lymphomas Best Pan-B cell marker
CD21 Follicular dendritic cells Dendritic cell sarcoma Defines lymphoid follicles in CD21+
FDC meshworks
CD23 Follicular dendritic cells, some CLL
B cells
CD25 T cells, Mast cells CTCL IL2R (CD25) may be drug target in
CTCL
CD30 Activated T cells CD30+ large cells in LPD Confirms CD30+ LPD
BCL2 All lymphocytes EXCEPT follicle Strongly positive in DLBCL; Absent pcFCL and reactive lymphoid follicles
center B cells in most pcFCL negative
BCL6 Follicle center B cells pcFCL, DLBCL (dim) Evaluation of B cell lymphomas;
strongly positive in FCL
bF1 Alpha/Beta T cells Alpha/Beta tumors usually positive; Confirms Alpha/Beta tumors if
Gamma/Delta tumors negative positive
pcDLBCL primary cutaneous diffuse large B-cell lymphoma, pcMZL extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid
tissue, primary cutaneous marginal zone lymphoma, pcFCL primary cutaneous follicle center lymphoma, CTCL cutaneous T-cell lymphoma,
CLL chronic lymphocytic leukemia/lymphoma, LPD lymphoproliferative disease, MF mycosis fungoides, FDC follicular dendritic cell

21 Lymphoid Antigens 49
Fig. 21.1 CD8+ T cells in cutaneous hypersensitivity reaction Fig. 21.3 CD25+ T lymphocytes in mycosis fungoides
Fig. 21.2 CD20+ B cells in primary cutaneous follicle center lymphoma Fig. 21.4 CD30+ large cells in lymphomatoid papulosis
22 Lymphoid Follicles in Hyperplasia
and Neoplasia
Cutaneous lymphoid follicles may be observed in cutaneous of mucosa associated lymphoid tissue type/marginal zone
lymphoid hyperplasia and are characteristically present in lymphoma and follicle center lymphoma).
the low grade B cell lymphomas (extranodal B-cell lymphoma
Extranodal Marginal Zone B−Cell Lymphoma of

CB CC Mncosa−Associated Lymphoid Tissne (MALT); pcMZL
IB
Reactive
Lymphoid Mantle Zone Neoplastic Marginal Zone Cells:
BCL2+ CD5−
Follicle BCL6− CD10−
CD10− IB BCL6−
CD5−/+ CB, CC BCL2+
IB
CB, CC
FDC: CD21+
FDC: CD21 FCC: BCL6+
FCC: CD20+
CD10+
CD10+ BCL2−
CD5−
BCL2−
BCL6+
IB = Immunoblast
CB = Centroblast
CC = Centrocyte
FDC = Follicular Dendritic Cell IB
FCC = Follicle Center Cell CB, CC
pcFCL = Primary Cutaneous Follicle
Center Lymphoma CD21+
FDC:
Neoplastic
pcFCL FCC: BCL6+
CD10+
BCL2−/+
Fig. 22.1 Lymphoid follicle structure in lymphoid hyperplasia and Occasionally the neoplastic BCL6−, BCL2+ marginal zone B cells will
B cell lymphoma. Reactive lymphoid follicles usually have round or infiltrate or colonize the lymphoid follicle, splaying the BCL6+, BCL2−
oval follicle centers with compact central collections of BCL6+, BCL2− follicle center cells. The lymphoid follicles in follicle center lymphoma
B cells. The lymphoid follicles of marginal zone lymphoma are sur- may be irregularly shaped as the neoplastic BCL6+ B cells out grow the
rounded by zones of plasma cells and or sheets of marginal zone B cells. normal follicular architecture

22 Lymphoid Follicles in Hyperplasia and Neoplasia 51
Fig. 22.2 Reactive lymphoid follicle, hematoxylin and eosin (H&E) Fig. 22.3 Reactive lymphoid follicle, BCL2 stain highlights all
stain lymphocytes except the follicle center B cells
Fig. 22.4 Reactive lymphoid follicle, CD21 stain highlights the folli- Fig. 22.5 Reactive lymphoid follicle, BCL6 stain highlights the folli-
cular dendritic cell meshwork cle center B cells
Part V
Epithelial Proliferations
23 Immunohistochemistry of Epithelial
Proliferations
Epithelial tumors that derive from the epidermis and adnexal to detect specific proteins that are associated with the tumor
structures may share keratinocytic cytology and epithelial cell origin are helpful in diagnosis.
growth patterns. Immunohistochemical stains using antibodies
Table 23.1 Immunohistochemical stains in the differential diagnosis of tumors with pilar, squamous, and adnexal origins
Squamous cell Sebaceous Eccrine Microcystic adnexal
Tricho epithelioma Basal cell carcinoma carcinoma carcinoma carcinoma carcinoma
BCL-2 + (Peripheral cells + (Diffuse) – (25 % focally +) + (Focal)
only)
BerEP4 + (60 %) + (Diffuse) – (+ in metastases) –
CK5/6 + + + + +
CK7 – – (60 %) – + + –
CK15 + (Focal) – – + +
CK17 + (Diffuse) – (Patchy or Rim +) + (Central)
CK20 + (Focal) – – – –
CK903 + + + + +
CAM 5.2 + (Rim) – + –
CD10 + (Stromal cells) + (60 %) –
CEA – – – (+ in normal + + (Inner cuticle)
glands)
EMA ± – + + + ±
Ki-67 <1 % 20–40 % 25–35 % 40–50 % 5%
P53 – + – + –
SMA ± – +
Blank spaces indicate the marker distribution is not well documented in this tumor

23 Immunohistochemistry of Epithelial Proliferations 55
Fig. 23.1 Cytokeratins 5/6 (CK5/6) in the epidermis. There is diffuse staining of the epidermal keratinocytes
Fig. 23.2 Cytokeratins AE1.3/CAM5.2 in epidermis and spindled squamous cell carcinoma. CK AE1.3/CAM5.2 stains the epidermis less
uniformly than CK5/6. CK AE1.3/CAM5.2 is positive in the underlying invasive spindled cells of squamous cell carcinoma
24 Actinic Keratosis
The acronym “SPAIN” corresponds to the histological SPAK (Spreading pigmented AK):
criteria: • Also uses SPAIN mnemonic
Solar elastosis • However, there is no parakeratosis
Parakeratosis – Instead “P” in SPAK = pigmentation of basal layer
Atypical basal layer keratinocytes keratinocytes
Inflammatory infiltrate • The clinical differential diagnosis includes lentigo or lentigo
No full thickness keratinocyte atypia (if there is full thickness maligna
keratinocytic atypia consider squamous cell carcinoma in situ)

24 Actinic Keratosis 57
Fig. 24.1 Actinic keratosis. There is marked parakeratosis, keratinocytic atypia, inflammation and solar elastosis
Fig. 24.2 Spreading pigmented actinic keratosis. Basal layer keratinocytic hyperpigmentation is present with keratinocytic atypia and solar
elastosis
25 Progression of Actinic Keratosis
to Squamous Cell Carcinoma
The evolution of sun-damaged skin to invasive squamous 2. Less common path: When transformed basal keratino-
cell carcinoma may occur along two main pathways. In both cytes do not have the capacity to breach the basement
cases, the basal layer keratinocytes are transformed, appear membrane zone, they fill all layers of the epidermis
cytologically atypical and proliferate at a higher rate than and replace the hair follicle epithelium, progressing to
normal. squamous cell carcinoma in situ. After the development
1. Most common path: When transformed basal keratino- of carcinoma in situ, if these tumor cells develop the
cytes have the capacity to breach the basement membrane capacity to breach the basement membrane zone, they
zone, they invade the dermis, usually as well-differentiated invade the dermis as moderately-differentiated squamous
squamous cell carcinoma. cell carcinoma.

25 Progression of Actinic Keratosis to Squamous Cell Carcinoma 59
SCCIS
AK SCCM
SCCW
Fig. 25.1 Schematic of squamous cell neoplasia and progression to Squamous cell carcinoma in situ is a more common precursor to mod-
invasion. Actinic keratosis (AK) is the most common direct precursor to erately differentiated invasive squamous cell carcinoma (SCCM)
well differentiated invasive squamous cell carcinoma (SCCW).
Fig. 25.2 Well differentiated, invasive squamous cell carcinoma Fig. 25.3 Well differentiated invasive squamous cell carcinoma. There
(right) adjacent to and actinic keratosis (left) is no in situ precursor, the precursor is actinic keratosis
26 Vulvar Dysplasia and Neoplasia
The differential diagnosis of abnormalities of the vulvar • Abnormal mitoses at all levels of the epithelium
epithelium includes inflammatory diseases and changes • May involve follicular epithelium and Bartholin’s ducts
caused by infection with human papilloma virus (HPV). • Occasionally progresses to HPV-associated SCC
Condyloma is the most common discrete lesion caused by • p16-positive
HPV. The changes may be subtle and resemble seborrheic Simplex (Differentiated) VIN – usually HPV-negative
keratosis or there may be extensive koilocytosis. There is • Parakeratosis, hyperkeratosis
significant histological overlap between dysplasia associated • Epidermal hyperplasia with slight to moderate basilar cell atypia
with inflammatory processes such as lichen planus or lichen – Enlarged squamous cells with prominent intercellular
sclerosus and HPV associated dysplasia. The separation of bridges, abundant brightly eosinophilic (PINK) cyto-
these processes into classic/bowenoid and simplex/differen- plasm, vesicular nuclei, and macronucleoli (e.g., well
tiated vulvar intraepidermal neoplasia (VIN) provides a differentiated)
framework for differential diagnosis. – Absence of maturation disarray, minimal nuclear
Condyloma pleomorphism
• Parakeratosis, hyperkeratosis, hypergranulosis, papillomatous • Large whorls of abnormally differentiated keratinocytes,
acanthosis occasionally with keratin pearls
• Koilocytosis with coarse keratohyaline granules • Scattered mitotic figures at base of epithelium
• Associated with HPV types 6 and 11 • Often associated with a lichenoid inflammatory infiltrate
• Mitoses restricted to the lower 1/3 of the epithelium (lichen planus, lichen sclerosus, lichen simplex
(VIN I) chronicus)
Classic (Bowenoid) VIN – often HPV-positive • Often progresses to HPV-negative SCC
• Parakeratosis, hyperkeratosis – Greater potential for progression to invasive SCC than
• Epidermal hyperplasia with maturation disarray, dyskera- classic VIN
tosis, cell crowding, scant cytoplasm and high N:C ratio – Look for small foci of stromal microinvasion into
(BLUE), irregular nuclear membranes papillary dermis
– Superficial cells may display koilocytic atypia • p53-positive

26 Vulvar Dysplasia and Neoplasia 61
Fig. 26.1 Condyloma Accuminatum. There is a papillomatous acanthosis of the epidermis and hyperkeratosis
Fig. 26.2 Vulvar Lichen Planus. There is a lichenoid inflammatory infiltrate, squamatization of basal layer keratinocytes and formation of a large
subepidermal cleft, the so-called Max-Joseph space
27 Nested Intraepidermal Proliferations
A nested intraepidermal pattern of growth may be observed tumors from keratinocytes and adnexal tumors from intraepi-
in several distinctive neoplasms derived from normal epidermal dermal adnexal elements.
elements: melanocytic tumors from melanocytes, squamous
Table 27.1 Differential diagnosis of nested intraepidermal proliferations

Atypical
Melanocytic Keratinocytic Pagetoid mitoses Dyskeratosis Other features
Malignant melanoma in situ + (Atypical) – + + –
Nevus + – −/+ – –
Squamous cell carcinoma in – + (Atypical) +/− + + Multinucleated cells;
situ Full thickness atypia
Extra mammary Paget’s – + (Intra-cytoplasmic + – – Intact basal layer
disease Mucin) keratinocytes;
Melanin pigment may
be present
Eccrine poroma – + (Monomorphous) – – – Pores with lining
cuticle; Round nuclei
Seborrheic keratosis – + (Monomorphous) – – – Pseudohorncysts; Flat
base

27 Nested Intraepidermal Proliferations 63
Fig. 27.1 Malignant melanoma in situ Fig. 27.3 Eccrine poroma
Fig. 27.2 Extramammary Paget’s disease Fig. 27.4 Seborrheic keratosis

28 Clinical Differential Diagnosis
of Histological Squamous Cell
Carcinoma In-Situ
The major histological criterion for the diagnosis of squamous SCCIS

cell carcinoma in-situ (SCCIS) is the presence of full thick- • Sun-exposed
ness epidermal keratinocytic maturation disarray (in marked • Viral infection
cases the epidermis appears similar viewed from the top or Epidermodysplasia Verruciformis
upside down). Other histological findings that help to secure • HIV population
the diagnosis are atypical mitoses and mitoses in the upper • HPV associated
levels of the epidermis and keratinocyte apoptosis. Several Bowenoid Papulosis
clinically distinct entities share the histopathological appear- • Clinically resembles warts, on genitalia
ance of squamous cell carcinoma in-situ as noted below. • Histologically identical to SCCIS
Bowen’s Disease Pedophyllin treatment of warts (non-neoplastic)
• Non sun-exposed skin (often mucosal) • Mitoses all arrested at the same stage

28 Clinical Differential Diagnosis of Histological Squamous Cell Carcinoma In-Situ 65
Fig. 28.1 Squamous cell carcinoma in situ Fig. 28.3 Epidermodysplasia verruciformis with viral cytopathic
changes in the superficial epidermis
Fig. 28.2 Bowen’s disease Fig. 28.4 Bowenoid papulosis

29 Basal Cell Carcinoma (BCC) Types
Basal cell carcinoma (BCC) types can be summarized as • Micronodular: multiple small dermal nodules
follows: • Morphea: hyalinized eosinophilic stroma with BCC cords
• Superficial of one to two cells
• Nodular • Infiltrative: like morphea but no eosinophilic collagen,
• Squamotized: focal keratinization instead there is a hyaluronic acid-rich fibrotic stroma
• Metatypical: foci of atypical squamous cells consistent • Basosquamous: collision tumor between BCC and SCC
with squamous cell carcinoma (SCC)
Fig. 29.1 Basal cell carcinoma, superficial and nodular types. Fig. 29.2 Basosquamous carcinoma, a collision between basal cell
carcinoma and squamous cell carcinoma

29 Basal Cell Carcinoma (BCC) Types 67
Superficial
Nodular
Micronodular
Basosquamous
Fig. 29.3 Types of basal cell carcinoma (BCC). Superficial BCC is basosquamous cell carcinoma is a collision tumor. BCC characteristically
attached to the epidermis, nodular BCC forms basaloid nodules in the is associated with a separation cleft between the palisaded basaloid
dermis, micronodular BCC is composed of multiple small nodules, and tumor cells and a basophilic mucin-rich dermis
Part VI
Adnexal Tumors
30 Sebaceous Neoplasms
Tumors with sebaceous differentiation range from The percentage of vacuolated cells as compared to the
hyperplasias that resemble normal sebaceous glands to percentage of basaloid cells is often helpful in distinguishing
carcinoma that are anaplastic or basaloid. Mature sebaceous the benign sebaceous neoplasms. Cytological atypia, matu-
elements have multivacuolated cytoplasm; the basaloid cells ration disarray and mitotic activity are features of sebaceous
surround the mature elements in the normal sebaceus gland. carcinoma.
Table 30.1 Differential diagnosis of sebaceous neoplasms

Histologic features
Sebaceous hyperplasia Rim of basaloid cells
Sebaceous adenoma <50 % basaloid component
>50 % mature sebaceous elements
Sebaceous epithelioma (Sebaceoma) >50 % basaloid component
<50 % mature sebaceous elements
BCC with sebaceous differentiation Diagnostic BCC at margins of sebaceous proliferation
Sebaceous carcinoma Atypical mitoses, SCCIS-like changes with sebaceous differentiation
Muir-Torre syndrome Multiple keratoacanthomas and difficult to classify sebaceous tumors
Absence of nuclear staining for MSH2, MSH6, MLH1, and/or PMS2
Protein is observed

30 Sebaceous Neoplasms 71
Fig. 30.1 Sebaceous hyperplasia Fig. 30.3 Sebaceous epithelioma
Fig. 30.2 Sebaceous adenoma Fig. 30.4 Sebaceous carcinoma

31 Nevus Sebaceus
Nevus sebaceus is a hamartoma of the pilosebaceous apocrine • Small and immature pilar-sebaceous apparati
apparatus that usually occurs on the scalp. • Apocrine glands
Histological Features of Nevus Sebaceus: Neoplasms Commonly Associated with Nevus Sebaceus
• Seborrheic keratosis-like epidermal hyperplasia • BCC
• Sebaceous glands enter directly into epidermis • Syringocystadenoma Papilliferum
Table 31.1 The histological differential diagnosis of syringocystadenoma papilliferum and hidradenoma papilliferum
Syringocystadenoma papilliferum Hidradenoma papilliferum
Connection with the epidermis + –
Plasma cells + –
Site Scalp Vulva
Scale crust – +
Benign epithelial proliferation with apocrine + +
Differentiation

31 Nevus Sebaceus 73
Hyperkeratosis
Epidermal Hyperplasia
Heterotopic
Apocrine Glands
Prominent Sebaceous
Glands, inserting directly
into epidermis
Poorly Formed
Follicular Units
Fig. 31.1 Schematic of nevus sebaceus
Fig. 31.2 Nevus sebaceus. This is a hamartoma (nevus) of the

Fig. 31.3 Nevus sebaceus. The epidermal hyperplasia may resemble
pilosebaceous apocrine unit
seborrheic keratosis
32 Eccrine and Apocrine Neoplasms
Eccrine Tumors • Ductal origin

Eccrine tumors are characterized by eosinophilic basement – Rare tumors because apocrine duct is very short
membrane material: • Secretory origin
• Ductal origin – Tubular Apocrine Adenoma
– Poroma: cuticle-lined lumens, pavement-like mono- – Syringocystadenoma Papilliferum (associated with Nevus
morphous proliferation of round cells Sebaceus)
– Porocarcioma: poroma-like, but with infiltrative growth • Connects to surface, plasma cells present
pattern, atypical mitoses, and tumor cell necrosis. – Hidradenoma Papilliferum (genital)
• Secretory origin • No connection to surface
– Acrospiroma/Clear Cell Hidradenoma: clear cyto- – Apocrine Carcinoma
plasm, solid and cystic • Variable atypia, infiltrative, papillary
– Clear Cell Hidradenocarcinoma: acrospiroma-like, but Mixed Tumors
with infiltration, atypical mitoses, and tumor cell necrosis. • Syringoma: “Tadpole” tubules, organoid stroma
• Other • Cylindroma: Basaloid “puzzle pieces” with eosinophilic
– Spiradenoma: basaloid, “blue balls” in the dermis droplets and mortar
• 2 cell populations • Microcystic Adnexal Carcinoma: Deeply infiltrative benign
• Granular, eosinophilic material in lumens appearing ducts
Apocrine Tumors
Apocrine tumors are characterized by decapitation secretion
(“snouts”):

32 Eccrine and Apocrine Neoplasms 75
Fig. 32.1 Eccrine Spiradenoma Fig. 32.3 Syringoma
Fig. 32.2 Cylindroma Fig. 32.4 Apocrine carcinoma

Part VII
Mesenchymal Tumors
33 Immunophenotype of Dermal
Spindled Cell Tumors
Spindled cell neoplasms of the dermis may have overlapping detection of proteins that characteristically are expressed by
histological features. Immunohistochemical stains allow the specific tumors.
Table 33.1 Differential diagnosis of dermal spindled cell tumors

CD34 Factor XIIIa CD31 CD10 S100 Vimentin MART-1
Melanoma – – – – + + +
Dermatofibroma – + – – – + –
DFSP + –/+ – – – + –
AFX – – – + –/+ + –
Leiomyoma – – – – – + –
DFSP dermatofibrosarcoma protuberans, AFX atypical fibroxanthoma (superficial malignant fibrous histiocytoma). All stains display internal
positive controls with normal cell types; e.g. CD31+ vasculature, S100+ melanocytes and dermal dendritic cells, MART-1 + melanocytes

33 Immunophenotype of Dermal Spindled Cell Tumors 79
Fig. 33.1 Dermatofibroma with characteristic dermal spindle cell Fig. 33.3 Dermatofibroscarcoma protuberans with dermal spindle
proliferation in a storiform growth pattern with epidermal hyperplasia cells in a storiform growth pattern and infiltrating subcutaneous fat. The
and basilar hyperpigmentation tumor cells are CD34-positive
Fig. 33.2 Dermatofibroma with multinucleate histiocytes and Fig. 33.4 Atypical fibroxanthoma with pleomorphic dermal spindled
characteristic wrapping around the reticular dermal collagen fibers and epithelioid cells in a fascicular growth pattern. The tumor cells are
CD10-positive
34 Fibrous Papule (Angiofibroma)
An angiofibroma is a common benign firm papule on the Also,

central face, often the nose. • Angiofibroma of face in Tuberous Sclerosis (develop-
Histology mental delay, epilepsy, angiofibromas, ash-leaf macules)
• Dermal spindled, stellate, and/or multinucleated fibroblasts • Pearly Penile Papule
• Collagenous stroma with perifollicular fibrosis • Acral angiofibroma (rare)
• Prominent blood vessels
• Absent or rare mitotic figures
Immunohistochemistry
• Factor XIIIa: +
• CD34: +/−
• S100: −

34 Fibrous Papule (Angiofibroma) 81
Fig. 34.1 Angiofibroma (fibrous papule) of the nose Fig. 34.3 Angiofibroma of the flank
Fig. 34.4 Acral angiofibroma
Fig. 34.2 Angiofibroma (fibrous papule) of the nose. The multinucleate

dermal fibroblasts may have a stellate morphology
35 Angiokeratoma
Angiokeratoma is represented by superficial dermal vascular • Angiokeratoma of Mibelli –dorsum of fingers and toes,
ectasia with surrounding epidermal hyperplasia and warty-like
hyperkeratosis. • Angiokeratoma of Fordyce –scrotum (less often on penis
Types: and vulva), associated with varicocele and hernia
• Angiokeratoma Circumscriptum - papules coalesce to • Solitary and Multiple Angiokeratomas –typically on
plaques on extremities lower extremities
– COBB syndrome = Angiokeratoma Circumscriptum,
Nevus Flammeus, Spinal Cord Angioma
• Angiokeratoma Corporis Diffusum – generalized
papules
– Fabry’s Disease (lysosomal storage disease, alpha-
galactosidase A deficiency)

35 Angiokeratoma 83
Fig. 35.1 Angiokeratoma
Fig. 35.2 Angiokeratoma. The ectatic vessels appear to be within epidermis but are separated by a rim of papillary dermis
Part VIII
Melanocytic Proliferations
36 Lentigo Versus Lentiginous
Lentigo is a term that describes a clinically distinct lesion Lentigo

that may be sub-classified as solar lentigo and lentigo simplex. • Increased basal layer keratonocyte pigmentation (as in ephelis)
Lentiginous is a descriptive term of a pattern of melanocytic • +/− hyperplasia of basal keratinocytes → budding (not in
growth as individual cells along the dermal epidermal junc- ephelis)
tion. Lentiginous melanocytic proliferation may be observed • +/− lentiginous melanocytic hyperplasia (not in ephelis)
in lentigo, however it is also observed in other processes Lentiginous
including dysplastic nevus, lentigo maligna, acral lentigi- • Increased density of melanocytes at base of epidermis
nous melanoma and mucosal melanoma. • No nesting (nest = three or more melanocytes)

36 Lentigo Versus Lentiginous 87
Fig. 36.1 Lentigo. There is keratinocytic hyperplasia and increased pigmentation of basal layer keratinocytes
Fig. 36.2 Lentiginous melanocytic proliferation. There are increased numbers of melanocytes at the base of the epidermis without nesting
37 Dermal Dendritic Melanocytic
Proliferations
There are several distinct forms of dermal dendritic melano- Nevus of Ito
cytic proliferations; the most commonly observed is the blue • Typically occurs on shoulder or upper arm
nevus. The melanocytes have delicately pigmented dendritic Nevus of Ota
processes and oval or round nuclei with delicately dispersed • Typically occurs on skin innervated by the ophthalmic
chromatin. and maxillary branches of the trigeminal nerve
Blue nevus Mongolian spot
• In addition to the common blue nevus there are several • Typically occurs in lumbosacral region
types of combined nevi that have a blue nevus component

37 Dermal Dendritic Melanocytic Proliferations 89
Fig. 37.1 Blue nevus. This proliferation of pigmented dendritic Fig. 37.3 Mongolian spot. There is a patchy distribution of pigmented
melanocytes is present in the interstitial reticular dermis and about dendritic melanocytes in the dermis
adnexal structures
Fig. 37.2 Blue nevus. The elongated pigmented cytoplasm is Fig. 37.4 Mongolian spot. The pigmented dendritic cells are
characteristic of blue nevus cells histologically similar to the cells of blue nevus
38 Dysplastic Nevi Criteria
The histological diagnosis of dysplastic nevus is based upon • Shoulder (intraepidermal component >3 rete beyond dermal
several histological features including the pattern of growth component)
and the host response to the tumor. The following criteria Minor Criteria, Need ³2/4
allow for consistent diagnosis of dysplastic nevi. Both major • Vascularity (prominent superficial vascular plexus)
criteria are required (except in the case of a junctional nevus • Fibrosis (eosinophilic concentric or lamellar)
there will be no shoulder), and at least two of the minor cri- • Inflammation (mononuclear cell inflammatory infiltrate
teria are required. After these criteria are met, the cytologic about superficial vascular plexus)
appearance of the melanocytes is evaluated to determine the • Bridging (nest expansion and fusion at dermal-epidermal
grade of atypia. junction)
Major Criteria, Need 2/2
• Lentiginous and nested cytologically atypical intraepidermal
melanocytic proliferation
Fig. 38.1 Dysplastic nevus major criteria: lentiginous and nested atypical Fig. 38.2 Dysplastic nevus major criteria: basilar proliferation of atypical
melanocyte proliferation melanocytes extending three rete beyond the dermal component
(“shoulder”)

38 Dysplastic Nevi Criteria 91
Fig. 38.3 Dysplastic nevus minor criteria: increased vascularity with Fig. 38.5 Dysplastic nevus minor criteria: superficial perivascular
endothelial cell hypertrophy lymphoid infiltrate
Fig. 38.4 Dysplastic nevus minor criteria: eosinophilic concentric Fig. 38.6 Dysplastic nevus minor criteria: bridging of rete by nests of
fibrosis atypical melanocytes
39 Dysplastic Nevi Melanocytic
Grading Criteria
The criteria for diagnosis of dysplastic melanocytic nevi are With increasing degree of atypia the size of the nuclei
defined as architectural and cytological. Cytological atypia is increase; a good reference for size is the nucleus of the mid-
required for the diagnosis of dysplastic nevus, however, there layer keratinocyte. The nuclear shape becomes more irregu-
is a range of degree of cytological atypia. When criteria for lar and the chromatin may be densely chromatic or clumped,
dysplastic nevi are met the tumors are graded based on the nucleoli may be prominent.
degree of melanocytic atypia.
Sickled Nucleus,
Slight /Mild Halo
Nuclear Enlargement,
Rhomboidal,
Moderate Dusty Pigmentation
Fully Evolved
Melanoma∼like
Severe Cytology
Fig. 39.1 Grades of melanocytic atypia in dysplastic nevus

39 Dysplastic Nevi Melanocytic Grading Criteria 93
Fig. 39.2 Slight (mild)

cytological atypia
in the junctional tumor cells
in dysplastic nevus
Fig. 39.3 Moderate cytological

atypia in the junctional tumor
cells in dysplastic nevus
Fig. 39.4 Severe cytological

atypia in the junctional
tumor cells in dysplastic nevus
40 Congenital Melanocytic Nevi
Melanocytic nevi with features of congenital onset may display usually compound or dermal and characteristically involve
several distinct patterns of growth. Congenital nevi are the reticular dermis.
Fig. 40.1 Congenital nevi. This schematic depicts

the variations of dermal growth patterns that may be
observed in congenital melanocytic nevi
Perivascular
Arranged around
blood vessels
May be subendothelial
Plaque
(Giant Hairy Nevus)
Maturation Can extend into fat

of melanocytes
Adnexal
(except
scalp) In sebaceous
epithelium
In arrector
pili muscle
Around hair follicles

40 Congenital Melanocytic Nevi 95
Fig. 40.2 Congenital nevus with a perivascular dermal growth pattern Fig. 40.4 Congenital nevus with extension around adnexal structures
and infiltration of the arrector pili smooth muscle
Fig. 40.3 Congenital nevus with a dermal component that diffusely

Fig. 40.5 Congenital nevus with a subendothelial growth pattern
infiltrates to form a plaque
41 Types of Combined Nevi
Following are the various types of combined nevi: – Deep pigmented nevus (plexiform/deep penetrating or
• Junctional, dermal, compound common or dysplastic inverted type A/clonal)
nevus combined with one of the following: • Other combinations with or without a common nevus
– Blue nevus (the most common) component
– Spindled and epithelioid cell nevus (Spitz or pigmented
spindled cell nevus [PSCN])

41 Types of Combined Nevi 97
Fig. 41.1 Compound deep penetrating/plexiform nevus. This is a Fig. 41.3 Inverted type A nevus
combined nevus with deep pigmented elements
Fig. 41.2 Compound combined congenital and blue nevus Fig. 41.4 Deep penetrating/plexiform nevus
42 Benign Melanocytic Proliferations
with Pagetoid Spread
Pagetoid spread is defined as an individual cell prolifera- The acronym PSPREAD highlights the types of tumors
tion in the upper levels of the epidermis, similar to the that may display pagetoid spread
pattern of epidermal involvement by Paget’s disease of Pediatric (nevus in infant, <5 years old; congenital nevus)
the breast. When the melanocytes have marked cytologi- Spitz nevus
cal atypia, pagetoid spread is considered a major criterion Pigmented spindled cell nevus
for the diagnosis of melanoma-in-situ. There are sev- Recurrent nevus
eral types of benign melanocytic proliferations that also Excoriated nevus
display pagetoid spread and can be distinguished from Acral nevus (MANIAC = melanocytic acral nevus with
melanoma. intraepidermal ascent of cells)
Dysplastic nevus

42 Benign Melanocytic Proliferations with Pagetoid Spread 99
Fig. 42.1 Pigmented spindled cell nevus with pagetoid spread of individual melanocytes in the epidermis
Fig. 42.2 Melanocytic acral nevus with intraepidermal ascent of cells (MANIAC)
Part IX
Reporting Melanoma
43 Invasive Primary Cutaneous Melanoma
Radial Growth Phase (RGP) • Stromal changes (desmoplastic)

• Single cell dermal invasion • Papillary/reticular dermis, fat (Clark level III, IV, V)
• Small invasive nests (dermal nests smaller than intraepidermal
nests) Table 43.1 Primary cutaneous melanoma Types
• No dermal tumor cell mitoses % of cases RGP VGP
• Inflammatory infiltrate SSM 70 % + –/+
• Papillary dermis (Clark level II) LMM 3% + –/+
Vertical Growth Phase (VGP) ALM 2% + –/+
• Expansile nodule NM 25 % – + (pure VGP melanoma)
• Nests in dermis larger than epidermis SSM superficial spreading melanoma, LMM lentigo maligna melanoma,
• Dermal mitoses ALM acral lentiginous melanoma, NM nodular melanoma

43 Invasive Primary Cutaneous Melanoma 103
Fig. 43.1 Superficial spreading melanoma with radial growth phase Fig. 43.3 Acral lentiginous melanoma in situ
and vertical growth phase
Fig. 43.2 Desmoplastic lentigo maligna melanoma with radial growth Fig. 43.4 Nodular melanoma is always a purely vertical growth phase
phase and vertical growth phase tumor
44 Measuring Melanoma Thickness
Primary tumor thickness is the most powerful prognostic measured perpendicular to the skin surface across the largest
indicator in patients with cutaneous melanoma. Adhering to diameter of the polypoidal projection.
consistent methods for measuring and reporting primary Guidelines for measuring primary melanoma tumor
tumor thickness is critical for patient care. The measurement thickness:
of tumor thickness is done at the microscope using an • Use a microscope with an intraocular micrometer and
intraocular micrometer. The microscope has a calibration calibration table
table that allows for conversion of the measurement in the • Measure perpendicular to the epidermal surface from the
micrometer to the actual measurement in millimeters. The top of the stratum granulosum to the deepest dermal mel-
primary tumor thickness is measured from the top of the epi- anoma cell
dermal granular cell layer to the deepest invasive melanoma • Do NOT include tumor cells within the adventitial dermis,
cell in the dermis. If the thickest region of tumor is associ- within perineural spaces, or within vessels in this
ated with overlying ulceration, the measurement is taken measurement
from the base of the ulcer to the deepest melanoma cell. • If there is an ulcer over the thickest part of the tumor,
Melanoma cells that extend along adnexal structures, nerves measure from the most superficial viable tumor cell to the
or vessels are not used for this evaluation. In the case of a deepest dermal melanoma cell
tumor with polypoidal architecture, the tumor thickness

44 Measuring Melanoma Thickness 105
Fig. 44.1 Measuring primary cutaneous melanoma thickness. The thickness. In this case, the tumor thickness, also known as the Breslow
melanoma cells in this schematic (brown circles) are present in the measurement, is taken from the top most viable cell beneath the ulcer to
epidermis, in the dermis beneath a focus of ulceration, along the edge of the deepest melanoma cell that is not associated with adnexal structures.
a hair follicle and as a microscopic satellite in the subcutaneous fat. The Microscopic satellites are not included in the Breslow measurement
black line indicates the appropriate location for measuring the tumor
45 Melanoma Regression
The presence of regression in primary melanoma is associ- melanoma in the epidermis or dermis. The criteria for
ated with an increased risk of metastasis, particularly in thin reporting regression are as follows:
melanoma. The most consistent correlations with prognosis • Focal complete absence of melanoma cells in the epidermis
occur when strict definitions in evaluating regression are AND dermis within or adjacent to an invasive melanoma
adhered to. Regression is characterized by complete absence • Often associated with a thin epidermis and underlying
of melanoma cells in the epidermis and dermis, flanked by fibrosis, increased vascularity, chronic inflammation, and
melanophages

45 Melanoma Regression 107
Epidermis
Pigment-Laden
Macrophages Dermis
Fibrosis
Vascularity
Vertical Growth
Phase
Focus of Radial Growth Phase
without Melanoma in Dermis
AND
without Melanoma in Epidermis
Fig. 45.1 Regression in primary cutaneous melanoma. The melanoma flanked by melanoma. This is the regressed focus. The presence of
cells (brown circles) are present in the epidermis and dermis. There is a regression is associated with an increased risk of metastasis
region in the center that lacks tumor in the epidermis and dermis, and is
46 Counting Melanoma Mitoses
Mitogenicity is an important prognostic factor in patients – Scan the H&E stained tissue section for the region of
with thin primary cutaneous melanoma. In the American the dermal tumor with the greatest number of mitotic
Joint Commission on Cancer (AJCC) seventh edition mela- figures → this is the starting point of the count. Count
noma staging system, mitoses, ulceration and tumor thick- the next consecutive high power fields till one square
ness form the foundation for staging thin primary cutaneous millimeter has been evaluated. (Each microscope is
melanoma. Studies demonstrating the prognostic value of different; 1 mm squared is four fields at 40× in some
mitogenicity used the “hot spot” technique for quantitation. microscopes.)
The AJCC Melanoma Staging Committee recommends the • Report the number of mitotic figures counted per mm2
use of the hot spot method with reports containing the number • If only one mitosis is found in any field, report this as
of mitoses counted in a square millimeter. This is accom- 1 mitosis/mm2
plished by examination of routine hematoxylin and eosin – Do NOT report as <1 mitosis/mm2
(H&E) stained tissue sections; exhaustive tissue sectioning is • If no mitoses are identified in the vertical growth phase,
not necessary. report this as 0 mitoses/mm2
• Use the “hot spot” method: – Do NOT report as <1 mitosis/mm2

46 Counting Melanoma Mitoses 109
1 mitosis/mm2
Fig. 46.1 Schematic of a melanoma that is reported as 1 mitosis/mm2. evaluation. While this tumor is larger than 1 mm2 total volume, there is
The melanoma cells (brown circles) are observed in the epidermis and one mitosis in the “hot spot” region of 1 mm2. This case is reported as
the dermis. Two tumor cells in mitosis (brown circle with black aster- 1 mitosis/mm2 (not <1 mitosis/mm2)
isk) are present. Intraepidermal tumor cells are not included in the
47 Reporting Tumor Infiltrating
Lymphocytes
The presence of many tumor infiltrating lymphocytes (TILs) Absent

in primary cutaneous melanoma is associated with a better • Lymphocytes may be present but DO NOT infiltrate the
prognosis. The degree of lymphocytic interaction with the melanoma. For example they may be around vessels, in a
tumor cells is graded as “brisk”, “non-brisk” or “absent” as fibrotic zone, or surrounding but not infiltrating the
defined below: melanoma
Brisk • There are no lymphocytes in association with any part of
• TILs present throughout the substance of the vertical the VGP
growth phase or infiltrating across the entire base of the • There is a dermal nodule of melanoma without
vertical growth phase (VGP). Lymphocytes must be inflammation
directly apposed to melanoma cells.
Non-Brisk
• TILs present in one or more foci of vertical growth phase

47 Reporting Tumor Infiltrating Lymphocytes 111
Brisk
Non-Brisk
Absent
Vessel
Fibrotic zone
Fig. 47.1 Schematic of tumor infiltrating lymphocytes (TILs) in primary In non-brisk infiltrates the interaction between the TILs and melanoma
cutaneous melanoma. In a brisk pattern the TILs (black small circles) cells is more patchy or focal. In infiltrates termed absent, lymphocytes
infiltrate throughout the vertical growth phase (VGP) or all along the may be present but do not interact with the melanoma cells
peripheral margin, touching the melanoma cells (brown circles).
48 Lentigo Maligna,
Lentigo Maligna Melanoma In Situ and
Lentigo Maligna Melanoma
The spectrum of severely atypical melanocytic proliferations • Epidermal atrophy

in sun-damaged skin of the elderly ranges from a prolifera- • Solar elastosis
tion of scattered individual cells along the dermal epidermal Lentigo Maligna Melanoma In Situ (LMMIS)
junction (lentigo maligna), to a dense intraepidermal prolif- LM and at least 2 of the 3 following criteria:
eration of cytologically atypical tumor cells with nesting, • Pagetoid spread of atypical melanocytes
confluence and pagetoid spread (lentigo maligna melanoma • Intraepidermal melanocytic nests
in situ). When the tumor cells invade the dermis, this is inva- • Confluence of cytologically atypical melanocytes along
sive melanoma. Below are the criteria for distinguishing the dermal-epidermal junction
these three steps in melanocytic neoplasia. Lentigo Maligna Melanoma
Lentigo Maligna (LM) • LMMIS and dermal invasion by atypical cells
• Atypical lentiginous melanocytic hyperplasia with focal
confluence

48 Lentigo Maligna, Lentigo Maligna Melanoma In Situ and Lentigo Maligna Melanoma 113
Fig. 48.1 Lentigo maligna melanoma in situ (LMMIS) with melano-

cytic nesting and confluence
Fig. 48.2 Lentigo maligna melanoma in situ (LMMIS) with melano-
cytic nesting and pagetoid spread
Table 48.1 Characteristics of LM, LMMIS, LMM

Lentigo maligna (LM) LM melanoma in-situ (LMMIS) LM melanoma (LMM)
Macular pigmented lesion on + + +
sun-exposed skin
Focal papule – – +
Epidermal atrophy + + +
Solar elastosis + + +
Atypical lentiginous melanocytic + + +
hyperplasia
Intraepidermal nesting – +/–a +/–
Pagetoid growth – +/–a +/–
Confluence – +/– +/–
Dermal component – – +
a
At least two of these three features are present in LMMIS
Part X
Special Stains
49 Histochemical Stains
In contrast to immunohistochemical stains which rely upon use chemical reactions to detect tissue specific elements.
antibodies to detect specific antigens, histochemical stains
Table 49.1 Commonly used histochemical stains in the evaluation of cutaneous disease
Stain Components stained Examples of common uses
Alcian Blue Acid dermal mucins Lupus, dermatomyositis, myxedema
Brown Hopps (tissue gram stain) Gram-positive: blue gram-negative: red Necrotizing fasciitis
Colloidal Iron Acid mucins Lupus, dermatomyositis, myxedema
Chloracetate Esterase (Leder) Mature myeloid cells/granulocytes Acute myelogenous leukemia, granulocytic sarcoma
Elastic Elastic fibers Perforating disorders, pseudoxanthoma elasticum,
anetoderma
Fontana-Masson Melanin, neuroendocrine secretory granules Post-inflammatory hyperpigmentation, vitiligo
Giemsa Mast cells, protozoa Urticaria pigmentosa, leishmaniasis
GMS (Grocott’s Methenamine Fungi Deep fungal infections
Silver)
Mucicarmine Epithelial, Mucin, and acid Mucin Adenocarcinoma, wall of Cryptococcus
PAS (Periodic Acid-Schiff) Glycogen, basement membrane zone glycoproteins, Onychomycosis
sialomucins
PAS-D (PAS-Diastase) Same as above but diastase breaks down glycogen Lupus, deep fungal infections
Toluidine Blue Acid mucins, mast cells Lupus, dermatomyositis
Trichrome Collagen Perforating disorders
Von Kossa Calcium Calciphylaxis

49 Histochemical Stains 117
Fig. 49.1 Elastic tissue stain in elastosis perforans serpiginosa Fig. 49.3 Mucicarmine stain marks intracytoplasmic mucin (pink) in
extramammary Paget’s disease
Fig. 49.2 Giemsa stains intracytoplasmic organisms in leishmaniasis Fig. 49.4 von Kossa stain highlights perivascular and interstitial
calcification (brown-black) in calciphylaxis
50 Immunohistochemical Stains
Immunohistochemistry is a valuable supplement to

hematoxylin and eosin staining that uses tagged antibodies
to detect tissue specific proteins.
Table 50.1 Immunohistochemical stains in dermatopathology

Stain Components stained Uses
CD1a Intraepidermal Langerhans cell and some dermal dendritic Langerhans cell histiocytosis
cells
CD34 Endothelial cells, hematopoietic progenitor cells, dermal Vessels and stromal elements
dendritic cells
CD68 Histiocytes General marker of histiocytes, not specific
CD163 Histiocytes More specific for histiocytes than CD68
CEA Adnexal ducts Stains ductal differentiation in adnexal neoplasms
Cytokeratin Intermediate filaments of epithelial cells CK5/6: squamous cells
CK7: adnexa, breast
CK20: Merkel cells (punctate)
AE1.3: most carcinomas
CAM5.2: most carcinomas
CK903: high molecular weight keratin (HMWK), basal
and myoepithelial cells
D240 Lymphatic endothelium Lymphovascular invasion
Desmin Intermediate filaments of myocytes Tumors with muscle differentiation
EMA Sebaceous cells and other adnexal cells Tumors with sebaceous differentiation
Factor XIIIa Fibroblasts Tumors with fibroblastic differentiation
Fli-1 Endothelial cells Vascular tumors
GFAP (Glial filament Intermediate filaments of CNS cells Tumors with neural differentiation
sssociated protein)
HMB-45 Melanocytes Identification of melanoma and intraepidermal nevi
Ki-67 Cycling cells Proliferative index
LCA (Leukocyte All lymphoid cells Positive in almost all non-Hodgkin lymphomas
common antigen)
MART-1 Melanocytes Melanoma and nevi
Melan-A Melanocytes Melanoma and nevi
MITF Melanocytes and some histiocytes Melanoma and melanocytes (nuclear)
NKIC3 Selected neural crest dermal cells Some melanomas and neurothekoma
S100 Neural tissue, secretory components of adnexa, Melanoma, nevi, and clear cell adnexal carcinoma
melanocytes
SMA (Smooth muscle Smooth muscle, myoepithelial cells, myofibroblasts Smooth muscle tumors, glomus cell tumors, eccrine
actin) carcinoma
Vimentin Mesenchymal tissues and melanocytes Soft tissue tumor and melanoma
This table is not comprehensive, but includes many of the most commonly used immunohistochemical stains in dermatopathology

50 Immunohistochemical Stains 119
Fig. 50.1 CD1a stain highlights intraepidermal Langerhans cells Fig. 50.3 Cytokeratin 7 (CK7) in extramammary Paget’s disease.
There is staining of intraepidermal tumor cells. Note the rim of CK7
negative keratinocytes at the dermal epidermal junction
Fig. 50.2 CD34 stain marked the neoplastic cells in dermatofibrosarcoma Fig. 50.4 Cytokeratin 20 (CK20) in merkel cell carcinoma. There is
protruberans punctate dot-like perinuclear staining
120 50 Immunohistochemical Stains
Fig. 50.5 D240 and S100 combined stain allows for the identification Fig. 50.7 S100 stains intraepidermal melanocytes and Langerhans cells
of S100+ melanoma cells (pink) within D240+ lymphatics (brown)
Fig. 50.6 HMB-45 stains intraepidermal melanocytes Fig. 50.8 SMA stains perivascular smooth muscle
Glossary
Acantholysis Loss of intercellular coherence between Grenz Zone A narrow area of uninvolved papillary dermis
keratinocytes separating the epidermis from an underlying dermal
Acanthosis Epidermal hyperplasia with increased thickness cellular infiltrate or neoplasm
of stratum spinosum Hyperkeratosis Thickening of the stratum corneum
Apoptosis Programmed cell death characterized by shrink- Kamino Body Eosinophilic hyaline globules composed
age of the cell, condensation of chromatin, and nuclear of basement membrane material typically found in
fragmentation Spitz nevi at the dermal-epidermal junction or dermal
Bulla Intraepidermal or sub-epidermal cavity greater papillae
than 5 mm in diameter containing serous fluid and/or Karyorrhexis Fragmentation of the nucleus of a dying cell
inflammatory debris resulting in nuclear dust (apoptosis)
Civatte/Colloid Bodies Intraepidermal or superficial papillary Leukocytoclasis The destruction of leukocytes, particularly
dermal eosinophilic, round bodies, common in lichenoid neutrophils, resulting in nuclear dust
processes Mucin Dermal mucin: acid mucopolysaccharides (mostly
Corps Ronds Keratinocytes in stratum spinosum with eosino- hyaluronic acid); stains with alcian blue, colloidal iron,
philic cytoplasm and perinuclear halos of basophilic kera- or toluidine blue; PAS negative; occurs in connective tis-
tohyaline granules in acantholytic dyskeratosis sue diseases. Epithelial mucin (sialomucin): consists of
Dyskeratosis Abnormal, premature keratinization of indi- neutral and acid mucopolysaccharides; PAS positive and
vidual keratinocytes below the stratum corneum diastase resistant, mucicarmine positive
Epidermotropism The presence of cytologically atypical Munro’s Microabscess Small accumulation of degenerated
T-lymphocytes within the epidermis usually without neutrophils within the stratum corneum in psoriasis
associated spongiosis, characteristic of mycosis fungoides Orthokeratosis Hyperkeratosis without retention of kerati-
Erosion Incomplete loss of epidermis without epidermal nocyte nuclei
basement membrane zone damage Parakeratosis Hyperkeratosis in which stratum corneum
Exocytosis The presence of mononuclear cells within the contains retained keratinocyte nuclei
epidermis usually with associated spongiosis Pautrier Microabscess Intraepidermal accumulation of three
Giant Cell Foreign body giant cell: multinucleate giant cell or more cytologically atypical T-lymphocytes within the
with haphazard arrangement of nuclei. Touton giant cell: stratum spinosum
multinucleate giant cell with a ring of nuclei surrounding Plexiform Following existing neurovascular structures
a central area of non-foamy eosinophilic cytoplasm with a forming a plexus or network, web-like
peripheral wreath-like area of foamy cytoplasm Pseudo-Pautrier Microabscess Intraepidermal accumula-
Grains Remnant tiny pyknotic nuclei of keratinocytes in tion of three or more Langerhans cells and lymphocytes
superficial epidermis in acantholytic dyskeratosis within the stratum spinosum
Granulation Tissue Newly formed loose collagenous Pustule Intraepidermal or sub-epidermal space containing
tissue in healing wounds composed of fibroblasts, new fluid and inflammatory cells, usually neutrophils
capillaries, and an infiltrate of lymphocytes, plasma cells, Reticular Degeneration Severe intracellular edema re-
and macrophages sulting in bursting of keratinocytes and formation of a
K.S. Masterpol et al., Atlas of Essential Dermatopathology, 121

DOI 10.1007/978-1-4471-4471-7, © Springer-Verlag London 2013
122 Glossary
multilocular vesicle with septa composed of remaining Ulcer Complete loss of epidermis often with basement
cell walls, characteristic of viral exanthem membrane zone destruction
Spongiform Pustule of Kogoj Multilocular neutrophilic Vesicle A small bulla, less than 5 mm in diameter
pustule in upper stratum spinosum in psoriasis
Spongiosis Intercellular epidermal edema causing increased
space between keratinocytes
Index
A Blue nevus, 89
Acantholytic process Bowenoid papulosis, 64, 65
Darier’s disease, 26, 27 Bowen’s disease, 64, 65
description, 26
diagnosis, 26
epidermis, 26 C
Grover’s disease, 26, 27 Candida, 16
Hailey-Hailey disease, 26, 27 CK5/6. See Cytokeratins 5/6 (CK5/6)
Acral angiofibroma, 81 CK7. See Cytokeratin 7 (CK7)
Actinic keratosis CK20. See Cytokeratin 20 (CK20)
pigmented, 57 Combined nevi
SPAIN and SPAK, 56 congenital and blue nevus, 97
Adnexal anatomy deep penetrating/plexiform nevus, 97
cutaneous structures, 5 description, 96
eccrine unit, 4, 5 inverted type A nevus, 97
pilosebaceous apocrine unit, 4 Congenital melanocytic nevi
AJCC. See American Joint Commission dermal component, plaque, 95
on Cancer (AJCC) description, 94
American Joint Commission on Cancer extension around adnexal structures and infiltration, 95
(AJCC), 108 with perivascular dermal growth pattern, 95
Angiofibroma. See Fibrous papule with subendothelial growth pattern, 95
Angiokeratoma variations, dermal growth patterns, 94
description, 82, 83 Cutaneous adnexal structures, 5
types, 82 Cylindroma, 75
Apocrine carcinoma, 75 Cytokeratin 7 (CK7), 119
Apocrine tumors, 74 Cytokeratin 20 (CK20), 119
Aspergillosis Cytokeratins 5/6 (CK5/6), 55
acute angle branching, 18, 19
description, 18
fruiting body, 18 D
GMS, 18, 19 Darier’s disease, 26, 27
histology, 18 Deep fungal infections
Autoimmune blistering dermatoses blastomycosis, 20
bullous pemphigoid, 28, 29 chromomycosis, 20
dermatitis herpetiformis, 28, 29 coccidioidomycosis, 20
description, 28 cryptococcosis, 20
diagnosis, 28 lobomycosis, 20
pemphigus vulgaris, 28, 29 paracoccidioidomycosis, 20
phaeohypomycosis, 20
shapes and sizes, 20, 21
B zygomycoses, 20
Basal cell carcinoma (BCC) Demodex, 10, 11
basosquamous carcinoma, 66 Dermal dendritic melanocytic proliferations
description, 66 blue nevus, 89
superficial and nodular types, 66, 67 description, 88
Basic anatomy Mongolian spot, 89
dermis, 2 Dermal spindled cell tumors
epidermis, 2, 3 atypical fibroxanthoma, fascicular growth pattern, 79
skin, 3 dermatofibroma, 79
subcutaneous fat, 2 dermatofibroscarcoma protuberans, 79
Basosquamous carcinoma, 66 histological features, 78
BCC. See Basal cell carcinoma (BCC) immunohistochemical stains, 78
K.S. Masterpol et al., Atlas of Essential Dermatopathology, 123

DOI 10.1007/978-1-4471-4471-7, © Springer-Verlag London 2013
124 Index
Dermatophytes H
different clinical manifestations, 16 Hailey-Hailey disease, 26, 27
histology, 16 Henoch-Schoenlein purpura (HSP), 45
Dermis Herpes simplex virus
papillary, 2 cytopathic effect, 15
reticular, 2 epidermal intracytoplasmic edema, 14
Dysplastic nevi follicular involvement and vasculitis, 14
basilar proliferation, atypical melanocytes, 90 multinucleated cells, 14
cytologic appearance, melanocytes, 90 Histochemical stains
eosinophilic concentric fibrosis, 91 elastic tissue, elastosis perforans serpiginosa, 117
histological diagnosis, 90 evaluation, cutaneous disease, 116
lentiginous and nested atypical melanocyte Giemsa, leishmaniasis intracytoplasmic organisms, 117
proliferation, 90 mucicarmine, intracytoplasmic mucin, 117
rete bridging by nests, 91 von Kossa, perivascular and interstitial calcification, 117
superficial perivascular lymphoid infiltrate, 91 HPV. See Human papilloma virus (HPV)
vascularity with endothelial HSP. See Henoch-Schoenlein purpura (HSP)
cell hypertrophy, 91 Human papilloma virus (HPV), 12, 60
Dysplastic nevi melanocytic grading
degree, melanocytic atypia, 92
moderate cytological atypia, 93 I
severe cytological atypia, 93 Immunohistochemical stains
slight cytological atypia, 93 CD1a, intraepidermal Langerhans cells, 119
CD34, dermatofibrosarcoma protruberans, 119
CK7, extramammary Paget’s disease, 119
E CK20, Merkel cell carcinoma, 119
Eccrine and apocrine neoplasms D240 and S100, S100+ melanoma cells
carcinoma, 75 identification, 120
cylindroma, 75 in dermatopathology, 118
spiradenoma, 75 description, 118
tumors, 74 HMB-45, intraepidermal melanocytes, 120
Eccrine poroma, 63 S100, intraepidermal melanocytes and Langerhans cells, 120
Eccrine spiradenoma, 75 SMA, perivascular smooth muscle, 120
Eccrine tumors, 74 Interface dermatitis
Eccrine unit, 4, 5 dermatomyositis, 33
Epidermis description, 32
intermingled cell types, 2 diagnosis, 32
stratified squamous epithelium, 2 graft vs. host disease, 33
Epidermodysplasia verruciformis, viral cytopathic lupus erythematosus, 33
changes, 64, 65 toxic epidermal necrolysis, 33
Epidermolysis bullosa Invasive primary cutaneous melanoma
description, 24 acral lentiginous melanoma in situ, 103
dystrophic, 25 desmoplastic melanoma, 103
electron microscopy/immunohistochemistry, 24 nodular, 103
epidermis and dermis, 25 RGP and VGP, 102, 103
junctional, 25 superficial spreading, 102, 103
subclassification, 24
Epithelial proliferations
CK5/6, 55 L
cytokeratins AE1.3/CAM5.2, 55 Lentiginous melanocytic proliferation, 86, 87
description, 54 Lentigo, 86, 87
immunohistochemical stains, 54 Lentigo maligna (LM), 112, 113
Extramammary Paget’s disease, 63 Lentigo maligna melanoma (LMM), 112, 113
Lentigo maligna melanoma in situ (LMMIS)
characteristics, 113
F description, 112
Fibrous papule with melanocytic nesting and confluence, 113
acral angiofibroma, 81 with melanocytic nesting and pagetoid spread, 113
flank, 81 Lentigo vs. lentiginous
histology and immunohistochemistry, 80 description, 86
nose, 81 melanocytic proliferation, 87
Lichenoid dermatitis
colloid bodies, 35
G description, 34
GMS. See Gomori methenamine diagnosis, 34
silver (GMS) fixed drug reaction, 35
Gomori methenamine silver (GMS), 18, 19 lichen sclerosus, 35
Grover’s disease, 26, 27 wedge-shaped hypergranulosis, 35
Index 125
LM. See Lentigo maligna (LM) Nodular melanoma, 103

LMM. See Lentigo maligna melanoma (LMM) Non-infectious palisading granulomatous dermatitis
LMMIS. See Lentigo maligna melanoma description, 40
in situ (LMMIS) diagnosis, 40
Lymphoid antigens granuloma annulare, 41
CD20+ B cells, 49 necrobiosis lipoidica, 41
CD30+ large cells, 49 rheumatoid nodule, 41
CD8+ T cells, 49
CD25+ T cells, 49
description, 48 P
immunohistochemical analysis, 48 Pagetoid spread, benign melanocytic proliferations
Lymphoid follicles definition, 98
B cell lymphomas, 50 MANIAC, 99
BCL2 stain, 50 PSCN, 96
CD21 stain, 51 PSPREAD, 98
description, 50 Parasites
in lymphoid hyperplasia and B cell demodex, 10, 11
lymphoma, 52 scabies, 10, 11
spider, 10, 11
tick, 10, 11
M Pemphigus vulgaris, 26, 27
MANIAC. See Melanocytic acral nevus with Perforating dermatoses
intraepidermal ascent of cells (MANIAC) elastosis perforans serpiginosa, 38
Max-Joseph space, 61 folliculitis, 38
MCC. See Merkel cell carcinoma (MCC) Kyrle’s disease, 38
Melanocytic acral nevus with intraepidermal reactive collagenosis, 38
ascent of cells (MANIAC), 99 Pigmented spindled cell nevus (PSCN), 96
Melanoma mitoses Pilosebaceous apocrine unit
AJCC, 108 apocrine units, 4
mitogenicity, 108 hair follicles, 4
1 mitosis/mm2, 109 sebaceous glands, 4
Melanoma regression Pityrosporum ovale
description, 106 histology, 16
in primary cutaneous melanoma, 107 tinea versicolor, 16
Melanoma thickness measurement Porokeratosis
description, 105 clinical features, 30
guidelines, 104 histological features, 30
polypoidal architecture, 104 parakeratotic column, 31
primary tumor, 104 PSCN. See Pigmented spindled cell nevus (PSCN)
Merkel cell carcinoma (MCC), 119 Psoriasiform dermatitis
Mixed tumors, 74 description, 36
Mongolian spot, 89 diagnosis, 36
diffuse parakeratosis, 37
monro microabscesses, 37
N neutrophils, 37
Nail anatomy regular epidermal hyperplasia, 37
bed, 6, 7
eponychium, 6
matrix, 6, 7 R
root, 6 Radial growth phase (RGP), 102
unit, 7 RGP. See Radial growth phase (RGP)
Necrobiosis lipoidica, 41 Rheumatoid nodule, 41
Nested intraepioliferations
description, 62
differential diagnosis, 62 S
eccrine poroma, 63 Sarcoidosis, 41
extramammary Paget’s disease, 63 Scabies, 10, 11
malignant melanoma in situ, 63 Sebaceous adenoma, 71
seborrheic keratosis, 63 Sebaceous carcinoma, 71
Nevus sebaceus Sebaceous epithelioma, 71
description, 72, 73 Sebaceous hyperplasia, 71
differential diagnosis, syringocystadenoma Sebaceous neoplasms
papilliferum and hidradenoma papilliferum, 72 adenoma, 71
epidermal hyperplasia, 73 carcinoma, 71
hamartoma, pilosebaceous apocrine unit, 73 differential diagnosis, 70
histological features, 72 epithelioma, 71
neoplasms, 72 features, 70
126 Index
Sebaceous neoplasms (cont.) description, 110

hyperplasia, 71 non-brisk, 110
tumors, 70 in primary cutaneous melanoma, 111
Seborrheic keratosis, 63
Spider, 10, 11
Squamous cell carcinoma V
common paths, 58 Vasculitis and vasculopathy
description, 58 characteristics, 44
differentiated, 59 description, 44
neoplasia and progression, invasion, 59 Henoch-Schoenlein Purpura, 45
Squamous cell carcinoma in-situ monoclonal cryoglobulinemia, 45
Bowen’s disease, 64 perniosis, 45
description, 64, 65 purpura fulminans, 45
epidermodysplasia verruciformis, 64 Verruca vulgaris
Bowenoid papulosis, 64 HPV, 12
pedophyllin treatment, 64 hypergranulosis, 12
Subcutneous fat, 2 hyperkeratotic keratin, 13
Superficial and deep perivascular mononuclear/lymphoid infiltrate keratohyaline granule clumping, 12
description, 42 parakeratosis, 12
differential diagnosis, 42 parakeratotic tier, 13
erythema chronicum migrans, 43 Vertical growth phase (VGP), 102
polymorphous light eruption, 43 VGP. See Vertical growth phase (VGP)
Superficial fungal infections VIN. See Vulvar intraepidermal
candida, 16 neoplasia (VIN)
dermatophytes, 16 Vulvar dysplasia and neoplasia
onychomycosis, 17 classic (Bowenoid) VIN – often
pityrosporum ovale, 16, 17 HPV-positive, 60
tinea nigra, 17 condyloma accuminatum, 60, 61
tinea versicolor, 17 differential diagnosis, 60
simplex (differentiated) VIN – usually
HPV-negative, 60
T vulvar lichen planus, 61
Tick bites, 10, 11 Vulvar intraepidermal neoplasia (VIN), 60
TILs. See Tumor infiltrating lymphocytes (TILs)
Tumor infiltrating lymphocytes (TILs)
absent, 110 Z
brisk, 110 Zygomycoses, 20

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Atlas of Essential Dermatopathology

Kasia S. Masterpol • Andrea Primiani

ISBN 978-1-4471-4470-0 ISBN 978-1-4471-4471-7 (eBook)

Library of Congress Control Number: 2012954534

© Springer-Verlag London 2013

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

Atlas of Essential Dermatopathology is based on a sketchbook developed during

Boston, MA, USA Kasia S. Masterpol, MD

Part III Inflammatory, Non-Infectious

Part IV Nodular Lymphoid Proliferations

Part V Epithelial Proliferations

23 Immunohistochemistry of Epithelial Proliferations . . . . . . . . . . . . . . . . . . . . . . 54

Part VI Adnexal Tumors

Part VII Mesenchymal Tumors

33 Immunophenotype of Dermal Spindled Cell Tumors. . . . . . . . . . . . . . . . . . . . . 78

Part VIII Melanocytic Proliferations

36 Lentigo versus Lentiginous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

Part IX Reporting Melanoma

43 Invasive Primary Cutaneous Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102

Part X Special Stains

49 Histochemical Stains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116

2 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

Superficial Vascular Plexus

Eccrine Unit – Phases: Anagen (growth), Catagen (involution), Telogen

4 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

Fig. 2.1 The cutaneous Hair Shaft

Nail Nail root

6 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

Proximal Nail Fold

Basal Layer Squamous Epithelium

Nail Matrix Pad

10 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

12 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

14 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

Fig. 6.2 Sketch of viral

Dermatophytes (Microsporum, Trichophyton, Pityrosporum ovale (Malassezia)

16 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

18 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

Fig. 8.1 Aspergillus. The

Zygomycoses (Rhizopus, Absidia, Mucor) Cryptococcosis

20 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

Table 10.1 Subclassification of epidermolysis bullosa

24 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

Table 11.1 Differential diagnosis of acantholytic processes

26 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

Fig. 11.4 Pemphigus vulgaris. There is suprabasal acantholysis with

Table 12.1 Differential diagnosis of autoimmune blistering dermatoses

28 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

Clinical features Histological features

30 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

Interface dermatitis is characterized by an inflammatory pro-

Table 14.1 The differential diagnosis of interface dermatitis

32 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

Fig. 14.1 Toxic epidermal necrolysis. There is full thickness epider-

Table 15.1 Differential diagnosis of lichenoid dermatitis

34 K.S. Masterpol et al., Atlas of Essential Dermatopathology,

Fig. 15.1 Lichenoid dermatitis. There is wedge-shaped hypergranulo-

Fig. 15.4 Fixed drug reaction. There is extensive epidermal dyskerato-

Table 16.1 Differential diagnosis of psoriasiform dermatitis