ETAS_05 dermatopath

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  • 1. 5 Dermatopathology Christine J. Ko, MDC o n t e n t s5.1 Normal Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1555.2 Stains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1565.3 Immunohistochemistry . . . . . . . . . . . . . . . . . . . . . . . . . 1575.4 Acantholytic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . 1585.5 Adnexal/Epithelial Neoplasms . . . . . . . . . . . . . . . . . 1605.6 Alopecias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1685.7 Bullous Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1685.8 Cysts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1695.9 Deposition Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1715.10  Drug Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1735.11  Fat Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1745.12 Fibrous/Fibrohistiocytic Disorders . . . . . . . . . . . . . 1755.13 Genodermatoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1795.14 Granulomatous Disorders . . . . . . . . . . . . . . . . . . . . . . 1805.15 Histiocytoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1815.16 Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1825.17 Inflammatory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1865.18 Lymphomas and Markers . . . . . . . . . . . . . . . . . . . . . . 1925.19  Melanocytic Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . 1955.20 Muscle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1985.21 Neural . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1995.22 Pagetoid Spread . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2015.23 Palisading Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . 2025.24 Vascular . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2035.25 Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2065.26 Clues for Board Purposes . . . . . . . . . . . . . . . . . . . . . . 2105.27 “Bodies” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212 Dermatopathology  153
  • 2. Committed to Your Future For practice exam questions and interactive study tools, visit the Dermatology In-Review Online Practice Exam and Study System at DermatologyInReview.com/GaldermaSponsored by
  • 3. 5.1 NORMAL SKINApocrine Glands • Decapitation secretion • Found in axillae, anogenital, external ear canal (ceruminous), eyelid (Moll’s), breast (mammary) • Apocrine glands have an inner layer of secretory cells that vary in height and demonstrate “snouts” of apocrine secretion with a layer of myoepithelial cells surrounding the glands • Stain with gross cystic disease fluid protein 15 (GCDFP-15) u TIP • Also stain with keratin AE1 (stains ducts), CAM 5.2, EMA aeen ectopically in nevus S sebaceus (a nice clue)Eccrine Glands • Merocrine secretion u TIP • Eccrine glands are composed of one distinct layer of cells with a resent all over the body P 2 populations, clear cells and darker cells; myoepithelial cells except on vermilion of lips, glans, labia minora, nail beds, surround glands, but are often difficult to appreciate inner prepuce • Stain with S100, CEA, CAM 5.2Sebaceous Glands • Holocrine secretion •   eibomian and Wolf (on eyelid), Fordyce (on vermilion, oral/mucosae), Tyson (on penis), M Montgomery (on nipple)Hair Follicle • Infundibulum = portion above insertion of sebaceous duct; identical to normal epidermis in keratinization pattern; desmoglein-3 positive in basal layer • Isthmus = portion between insertions of sebaceous duct and arrector pili; trichilemmal keratinization; desmoglein-3 positive in all layers • Lower portion = from arrector to the base of follicle u TIP • Inner root sheath not present at isthmus a ayers of the lower portion (from L • Epidermis and infundibulum undergoes keratinization with outer to inner): fibrous root sheath, keratohyaline granules (basophilic); outer root sheath glassy/vitreous layer, outer root undergo trichilemmal keratinization (without forming sheath, inner root sheath (Henle, granules) in the isthmus; lower part of the follicle’s inner Huxley, cuticle of inner root sheath), hair cuticle, hair cortex, hair medulla; root sheath undergoes keratinization with trichohyaline desmoglein-1 positive in inner root granules (eosinophilic); hair keratinizes without forming sheath and innermost part of outer granules and forms hard keratin root sheath • Trichilemmal carcinoma stains with keratin 17 and c-erb-b2 • Proliferating trichilemmal cyst stains with cytokeratin 7 u TIP an pachyonychia congenita type I INail Bed (Jadassohn-Lewandowsky), keratins • Expresses keratin 6, 16, 17 6a and 16 are mutated an pachyonychia congenita type II I (Jackson-Lawler), keratins 6b and 17 are mutated, and patients have multiple steatocysts Dermatopathology  155
  • 4. 5.2 STAINSBodian • Nerve fibers blackFeulgen • DNA magentaFontana Masson • MelaninFoote’s or Snook’s • Reticulin fibers blackGiemsa • Mast cell granules purple (it is the heparin in the mast cells that is staining) • LeishmaniaLeder • Mast cell granules redMasson Trichrome • Collagen blue/green, muscle/nerve/keratin redMethyl-green Pyronin • RNA pink, DNA greenPerls (Prussian Blue) • Iron/hemosiderin bright blue u TIPPTAH (Phosphotungstic Acid Hematoxylin) a  tains the inclusions in S • Stains fibrin infantile digital fibromatosisFor Amyloid • Congo red (stains red, green birefringence on polarization) • Crystal violet (more specific; stains purple) • Thioflavin T (fluoresces green-blue) • Acid orcein Giemsa (stains sky blue)For Bacteria • McCallum-Goodpasture • Brown-Brenn • Brown-Hopps • Ziehl-Neelsen and Fite-Faraco for acid-fast bacteriaFor Calcium • Von Kossa (blue-black) • Alizarin red (red) • Pentahydroxy flavanol (fluoresces) • Aldehyde fuchsin (brown)156  2011/2012 Dermatology In-Review l Committed to Your Future
  • 5. For Elastic Tissue • Verhoeff von Gieson (blue-black) • Gomori’s aldehyde-fuchsin (purple) • Orcein-Giemsa (black)For Fat (Need Fresh/Frozen Tissue) • Scarlet red • Oil red O • Sudan black (also stains lipofuscin) • Osmium tetroxide (differentiates animal fat from mineral oil)For Fungi • PAS • GMS (Gomori methenamine silver)For Mucin/Mucopolysaccharides (MPS) • Alcian Blue 2.5 (blue) - acid MPS • Alcian Blue 0.5 (blue) - sulfated MPS • Colloidal iron (blue) - acid MPS • Mucicarmine (pink) • Toluidine blue (blue) - acid MPSFor Mycobacteria • Ziehl-Neelsen • Fite-FaracoFor Nerve Fibers • Bodian (nerve fibers black) • PGP 9.5 • NeurofilamentFor Ochronosis • Cresyl violet or methylene blue stains the pigment blackFor Spirochetes • Silver stains like Warthin Starry or Dieterle or Steiner5.3 IMMUNOHISTOCHEMISTRY Table 5-1. Commonly Used Immunohistochemical Stains Antigen Major Targets Cytokeratin (AE1/AE3, NORMAL: Epidermis and adnexal epithelium 34BE12, MNF116, 5/6, etc.) USEFUL FOR: Squamous cell carcinoma S-100 protein NORMAL: Melanocytes, Langerhans cells, eccrine glands, chondrocytes, adipose tissue, nerves USEFUL FOR: Melanoma, adnexal tumors, neural tumors HMB-45 NORMAL: Melanocytes USEFUL FOR: Some melanomas, nevi Dermatopathology  157
  • 6. Table 5-1. Commonly Used Immunohistochemical Stains (cont) Antigen Major Targets MelanA/MART-1 NORMAL: Melanocytes USEFUL FOR: Melanoma, some nevi Mel-5 NORMAL: Melanocytes USEFUL FOR: Some melanomas/nevi, vitiligo Vimentin NORMAL: Tissue with mesenchymal derivation USEFUL FOR: Atypical fibroxanthoma, sarcomas, melanomas, some squamous cell carcinomas Desmin NORMAL: Smooth/skeletal muscle USEFUL FOR: Muscle tumors Smooth muscle actin (SMA) NORMAL: Smooth muscle, myofibroblastic cells USEFUL FOR: Smooth muscle tumors, some atypical fibroxanthomas Carcinoembryonic antigen NORMAL: Eccrine/apocrine glands (CEA) USEFUL FOR: Adnexal tumors, Paget’s disease of the breast, extramammary Paget’s Epithelial membrane antigen NORMAL: Sebaceous, eccrine, apocrine glands (EMA) USEFUL FOR: Sebaceous tumors, squamous cell carcinoma, epithelioid sarcoma, systemic (nodal) anaplastic large cell lymphoma Neuron-specific enolase NORMAL: Non-specific neuroendocrine marker (NSE) USEFUL FOR: Merkel cell carcinoma Chromogranin NORMAL: Neuroendocrine cells USEFUL FOR: Merkel cell carcinoma Synaptophysin NORMAL: Neuroendocrine cells USEFUL FOR: Merkel cell carcinoma Cytokeratin 20 NORMAL: Neuroendocrine cells USEFUL FOR: Merkel cell carcinoma, trichoepithelioma Factor VIII-related Antigen NORMAL: Endothelial cells, platelets, megakaryocytes USEFUL FOR: Vascular tumors CD31 NORMAL: Endothelial cells, stem cells USEFUL FOR: Dermatofibrosarcoma protuberans, vascular tumors Factor XIIIa NORMAL: Dermal dendrocytes USEFUL FOR: Dermatofibroma Cytokeratin 5/6 NORMAL: Epithelial cells P63 P63 USEFUL FOR: Primary cutaneous adnexal tumors; negative in metastatic adenocarcinomas TTF-1 NORMAL: Thyroid tissue USEFUL FOR: Lung carcinoma; negative in Merkel cell carcinoma5.4 ACANTHOLYTIC DISORDERSDarier’s Disease (Keratosis Follicularis) • Column of parakeratosis above a focus of acantholytic dyskeratosis (corps ronds and grains) u TIP a utosomal dominant, ATP2A2 gene that encodes the A sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA)158  2011/2012 Dermatology In-Review l Committed to Your Future
  • 7. Grover’s Disease • Often smaller foci than those in Darier’s, without the column of parakeratosisHailey-Hailey • “Full-thickness acantholysis,” the so-called dilapidated brick wall, although sometimes the upper layers of the epidermis are not acantholyticu TIPaAutosomal dominant, ATP2C1 geneParaneoplastic Pemphigus Figure 5-1. Darier’s Disease • Clinical presentation is with intractable oral u TIP ulcers/erosions, conjunctivitis, target-like lesions aOften there are several foci of acantholytic dyskeratosis,  (EM-like) sometimes with different patterns in different foci, for • Suprabasilar acantholysis (like PV) and EM-like example, one focus that appears more spongiotic with another that looks like PV and another that looks like changes (necrotic keratinocytes and vacuolar Dariers or Hailey-Hailey or superficial pemphigus change of the basal layer)u TIPantercellular and linear DEJ antibodies against desmoplakins I (250 kDa, 230 kDa bullous pemphigoid antigen 1), envoplakin (210 kDa), periplakin (190 kDa), 170 kDa antigen, PV Ag (130 kDa)Pemphigus Foliaceus (PF) • Intraepidermal acantholytic blister, through the subcorneal/granular layer, granular cells often appear more prominent • Differential includes bullous impetigo, subcorneal pustular dermatosis, pemphigus erythematosus Figure 5-2. Hailey-Hailey • Clues to PF rather than bullous impetigo are “cling-ons,” which are acantholytic cells that are still attached to the stratum corneum on the roof of the blister, and less neutrophils in the blister cavity •  Intercellular antibodies against desmoglein 1, 160 kDaPemphigus Vegetans • Variant of pemphigus vulgaris •  Marked hyperplasia of the epidermis with characteristic eosinophilic abscesses, acantholysis may be minimal Figure 5-3. Pemphigus Foliaceus Dermatopathology  159
  • 8. Pemphigus Vulgaris (PV) • Intraepidermal acantholytic suprabasal blister, non-dyskeratotic, with tombstoning of the basal layer •  Acantholysis extends down adnexae, unlike in Hailey Hailey •  Intercellular antibodies against desmoglein  3, 130 kDa Squamous Cell Carcinoma, Adenoid Type • Also called acantholytic SCC • Because of dyskeratosis and subsequent acantholysis, SCC’s may show tubular and Figure 5-4. Pemphigus Vegetans alveolar formations on histology; often, an AK of the acantholytic type is seen overlying the lesion Warty Dyskeratoma • Can look exactly like Darier’s, but ideally it is a larger lesion (solitary clinically) that sometimes has a cyst-like architecture 5.5 ADNEXAL/EPITHELIAL NEOPLASMS Acrospiroma • Includes hidroacanthoma simplex (located intraepidermally) (see Figure under Hidroacanthoma Simplex), poroma, dermal Figure 5-5. Warty Dyskeratoma duct tumor, hidradenoma (deeper dermis) • Poroma: Uniform blue cells coming off in a plate-like fashion off of the epidermis, ductal areas within • Hidradenoma: Clear cells and more basaloid/cuboidal cells peripherally, ductal areas Adenoid Cystic Carcinoma • Also fairly characteristic pattern • Cribiform pattern of epithelium and ductal areas Clear Cell Hidradenoma (Eccrine Hidradenoma, Eccrine Acrospiroma, Nodular Hidradenoma, Solid-cystic Hidradenomia) • Large, circumscribed, but not encapsulated • Occasionally connects to overlying epidermis or extends into subcutis • Biphasic cellular population: round cells with eosinophilic cytoplasm and oval vesicular nucleus or cells with clear cytoplasm with small dark eccentrically located nucleus Figure 5-6. Adenoid Cystic Carcinoma 160  2011/2012 Dermatology In-Review l Committed to Your Future
  • 9. • May contain some ducts; very few distinguishing features and may be a diagnosis of exclusion; distinguish from metastatic renal cell carcinomaCylindroma • Thought to be apocrine in origin • Upper dermis without connection to overlying epidermis • Multiple, puzzle-like lobules in jigsaw or mosaic pattern, each lobule has basement membrane (PAS positive, dense pink stroma) around it Figure 5-7. Clear Cell Hidradenoma • CYLD gene •  Brooke-Spiegler syndrome: multiple  trichoepitheliomas, cylindromas, spiradenomasDesmoplastic Trichoepithelioma • Quite different from conventional trichoepithelioma • Slight indentation of the epidermis; small areas look like syringomas • Narrow epithelial strands embedded in dense collagenous stroma, horn cysts, calcification frequently seen, symmetric; rounded base • Doesn’t penetrate like morpheaform BCC; lots of horn cysts and calcium Figure 5-8. Desmoplastic Trichoepithelioma deposits; no retraction artefactDilated Pore of Winer • Keratin-plugged, cystically dilated hair follicle, usually superficial, but can extend into subcutaneous fat • Lined by acanthotic epithelium, with buds of proliferation extending away as irregular strandsFibroepithelioma of Pinkus • Polypoid shape; basaloid epithelial strands, 2-3 cells thick, arising from many foci along the epidermis and anastomosing to compartmentalize the fibrous stroma Figure 5-9. Fibroepithelioma of Pinkus Dermatopathology  161
  • 10. Hidradenoma Papilliferum • Vulvar area • Well-demarcated nodule in dermis and may be continuous with overlying epithelium • Papillated projections into cystic spaces, decapitation secretionHidroacanthoma Simplex (IntraepidermalPoroma) • Hyperkeratosis with acanthosis • Epidermis shows discrete collections of regular tumor cells that resemble those of an eccrine poroma • Tumor cells can be spindle shaped also; Figure 5-10. Hidradenoma Papilliferum the dermis is unaffectedInverted Follicular Keratosis • Endophytic with whorls of maturing squamous epithelium (squamous eddies) near hair follicle ostium; some lesions contain horn cysts; no koilocytesIrritated Seborrheic Keratosis • Characteristic squamous eddies of eosinophilic squamous cells in a downward proliferation (endophytic) with minimal to mild inflammation at the base • Some say that this is the same as an inverted follicular keratosisKeratoacanthoma Figure 5-11. Hidroacanthoma Simplex • Crateriform architecture, symmetric, large central keratin plug, well-formed flanking collarette • Well-differentiated, often pale-staining, eosinophilic, glassy cytoplasm with tendency toward keratinization, no abnormal mitotic figuresMicrocystic Adnexal Carcinoma • “Syringoma gone mad”; grows deep without metastasizing • Round balls (syringoma-like) up high, and more linear and cord-like down low Figure 5-12. Inverted Follicular Keratosis162  2011/2012 Dermatology In-Review l Committed to Your Future
  • 11. • Numerous small to medium-sized squamous microcysts, superficially located, and solid strands of cells, many with ductular lumina, dense fibrous stroma surrounds all components and is more sclerotic in infiltrative areas • Perineural invasion frequently observedMixed Tumor of the Skin (ChondroidSyringoma) • Areas that look like cartilage with ductal/ adnexal structure-like cords/strands of cells • Multilobulated within deep dermis and/or subcutaneous fat Figure 5-13. Mixed Tumor of the Skin • Abundant stroma with basophilic pseudocartilaginous appearance • Lobules separated by fibrous septa • Nests and cords of cuboidal cells with copious eosinophilic cytoplasm and basophilic nuclei, tubuloalveolar structures lined by two or more rows of epithelial cellsMorpheaform Basal Cell Carcinoma (BCC) • Thin cords of basaloid cells, getting thinner as the cords go deeper; some retraction artefact may be present • Haphazard downward growth that infiltrates • Can resemble desmoplastic Figure 5-14. Nevus Sebaceus of Jadassohn trichoepithelioma, but often infiltrates deeper into the dermis •  Bcl-2 stains BCCs diffuselyMucinous Carcinoma • Dermal tumor that may extend into subcutaneous fat, with very characteristic, “floating” compartmentalized islands of tumor cells suspended in a lake of mucin • Tumor cells are sometimes vacuolated with eosinophilic cytoplasm and small hyperchromatic nuclei • MUST rule out metastatic cancerNevus Sebaceus of Jadassohn • Epidermal acanthosis and papillomatosis • Foci of abortive hair papillae • Sebaceous glands located abnormally high in dermis, opening directly onto surface, and can appear unrelated to hair follicle Dermatopathology  163
  • 12. • Has a different look pre-pubertal (smaller sebaceous glands) and post-pubertal (larger sebaceous glands) • A clue is apocrine glands in the reticular dermis • Tumors can arise within nevus sebaceus, with trichoblastoma thought to be the most common, followed by syringocystadenoma papilliferum, BCCPilomatricoma (Calcifying Epithelioma ofMalherbe) • Basaloid blue cells (matrical cells) and pale pink amorphous areas that on higher power have “shadows” Figure 5-15. Pilomatricoma of nuclei (shadow cells), areas of calcification or sometimes ossification • Mutations found in beta-catenin PEARL w ultiple pilomatricomas seen in  M Rubinstein-Taybi, Gardner’s (cyst-like pilomatricomas), Turner’s, sarcoidosis, sternal cleft and coagulation defects, myotonic dystrophy (Steinert’s) Proliferating Trichilemmal Tumor • Looks like a pilar cyst gone wild • Lobulated intradermal mass of squamous epithelium • Individual lobules with sharply defined Figure 5-16. Proliferating Trichilemmal Tumor and non-infiltrating border • May be surrounded by a thickened basement membrane • Striking peripheral palisading of lobule edges • Tricholemmal keratinization with absent granular layerSebaceous Adenoma • Lobules of sebocytes with rims of basal cells • May replace surface epithelium • Individual lobules mirror structure of normal sebaceous gland, periphery of lobule shows small germinative cells with scanty cytoplasm Figure 5-17. Sebaceous Adenoma164  2011/2012 Dermatology In-Review l Committed to Your Future
  • 13. • >50% lobule contains mature sebaceous cells • Sebaceous epitheliomas are more asymmetric and disorganized with >50% of cells being basaloid germinative cells • If there are mitoses, an infiltrative growth pattern, and atypical cells, think of sebaceous carcinoma • Associated with Muir-Torre syndromeSpiradenoma • “Blue balls in the dermis” (no epidermal connection) → tumor lobules in dermis and occasionally into subcutaneous fat • Lobules are intensely basophilic with cells Figure 5-18. Spiradenoma arranged in intertwining cords, dark and light cells • A clue is focal pockets of hyaline material within the cellular areas and lymphocytes peppering the islands • Now thought to be apocrineSyringocystadenoma Papilliferum • Papillated tumor with abundant plasma cells in the stroma • Invagination from overlying epidermis • Double-layered epithelium with outer zone of small cells and inner zone of tall columnar cells • May show decapitation secretion Figure 5-19. Syringocystadenoma PapilliferumSyringoma • Duct-like “tadpoles” and cords of peripheral blue cells around central clear cells in a fibrous stroma • Increased incidence in patients with Down’s • Clear-cell variant is associated with diabetes Figure 5-20. Syringoma Dermatopathology  165
  • 14. Trichilemmoma • Proliferation of outer root sheath • Small solitary lobule or group of lobules connected to epidermis with vertical growth • Peripheral palisading of lobules • Many of the tumor cells contain glycogen and have a clear cell appearance (PAS- positive) • At the base of each lesion is a thin red line mimicking the vitreous sheath of hair • Multiple ones seen in Cowden’sTrichoadenoma • In dermis, numerous horn cysts Figure 5-21. Trichilemmoma surrounded by eosinophilic epithelium • Well-defined fibroepithelial tumor composed of horn cysts and conspicuous fibrovascular stroma • Scattered islands of tumor cells • Midway between a trichoepithelioma and a trichofolliculoma in terms of differentiationTrichoblastoma • More primitive than trichoepithelioma; usually lacks horn cysts • Features similar to trichoepithelioma, but centered in mid dermis and can involve subcutaneous fat • Lobules of basaloid cells intimately Figure 5-22. Trichoadenoma associated with conspicuous fibromyxoid stroma • Clue is the papillary mesenchymal body, which resembles a very early hair bulb (follicular germ) surrounded by loose spindle cells, although this can be seen in trichoepitheliomasTrichodiscoma • Flattened epidermis, with lateral collarette • Unencapsulated, elliptical, loosely woven admixture of collagen, reticulin, and thin elastic fibers • Always topographically related to hair follicle • Seen in Birt-Hogg-Dube166  2011/2012 Dermatology In-Review l Committed to Your Future
  • 15. Trichoepithelioma • Numerous horn cysts both in dermis and within lobules of basaloid cells, complete keratinization, tumor cells indistinguishable from those of BCC, showing peripheral palisading, perilobular connective tissue sheath more conspicuous (more fibrotic) and associated with formation of papillary mesenchymal bodies (primitive hair bulbs), foreign body giant cell reaction to free keratin, clefts between stroma and stroma, and no clefts between cells and stroma; horn cysts occur Figure 5-23. Trichoepithelioma PEARLw R  asmussens syndrome: multiple trichoepitheliomas, cylindromas, and miliaw  Rombo syndrome: multiple trichoepitheliomas, milia, vermiculate atrophy, BCC, peripheral vasodilation and cyanosisTrichofolliculoma • Dilated hair follicle (cystic cavity) with granular layer and containing keratinous debris and hair shaft fragments • Arises from surface epithelium • Numerous hair follicles arise from its wall, each surrounded by a clearly defined perifollicular sheath Figure 5-24. Trichofolliculoma • Clinically has one or more silky white hairs extending out from lesionVerrucous Carcinoma • “Condyloma gone wild”; takes up one-half the size of the slide • Acanthotic papillary processes with massive hyperkeratosis and often parakeratosis • Endophytic component has well-differentiated squamous epithelium growing down into the underlying tissues as deeply penetrating, bulbous processes showing a characteristic “pushing” margin (in contrast to the infiltrative border of an ordinary SCC) • Keratinization is massive, with accompanying sinuses; no cytologic atypia Dermatopathology  167
  • 16. 5.6 ALOPECIASAlopecia Areata • Peribulbar lymphohistiocytic infiltrate around anagen follicles near dermal/ subcutaneous junction (“swarm of bees”) • There may be increased catagen hairs and miniaturized hairsAndrogenetic Alopecia • Scalp skin • Many follicles show diminished size (miniaturization) • Lack of inflammationDiscoid Lupus Erythematosus Figure 5-25. Discoid Lupus Erythematosus • Scalp skin often • Epidermal atrophy, follicular plugging, dense lymphohistiocytic periadnexal infiltrate, area of scarring • Vacuolar change at DE junction • Basement membrane thickening • Mucin in collagen bundles • Pigmentary incontinenceLichen Planopilaris • Focally dense perivascular and periadnexal lymphohistiocytic infiltrate • Focal areas of hypergranulosis, keratin plugging, vacuolar changes of basal layer of the follicular epithelium • Advanced disease shows fibrous scars vertically oriented • Adjacent interfollicular epithelium may show typical lichenoid infiltrate • Basal cell hydropic degeneration may or may not be present • Differential diagnosis is LE, which would not show normal epidermis between the folliclesPseudopelade of Brocq • Presence of normal epidermis and reduced numbers or absence of sebaceous glands • No evidence of inflammatory folliculitis • Vertically-oriented fibrous scarring replaces hair follicles, with arrector pili still attachedTrichotillomania • Trichomalacia → hair shafts fragmented, bent, and distorted • Pigmented casts u TIP5.7 BULLOUS DISORDERS aA clue to early BP is eosinophilic spongiosis and Bullous Pemphigoid (BP) eosinophils lined up along the DEJ • Subepidermal separation with eosinophils (but sometimes there is re-epithelialization at the base, so the blister can look intraepidermal) • A clue to early BP is eosinophilic spongiosis and eosinophils lined up along the DEJ • Rarely BP can be neutrophilic or “cell-poor” (non-inflammatory)168  2011/2012 Dermatology In-Review l Committed to Your Future
  • 17. • Linear IgG and C3 at the DEJ on direct immunofluorescence (DIF) • Two antigens: Bullous pemphigoid antigen-1 (BPAg-1) (230 kDa) and Bullous pemphigoid antigen-2 (BPAg­ 2) (180 kDa); the BPAg-2 is thought to be the pathogenic antigen - • Herpes gestationis can be indistinguishable from BP on biopsy but on DIF has linear C3 and less commonly IgGCicatricial Pemphigoid (CP) • Sparse inflammation, subepidermal separation, scarring of papillary dermis • Look for plasma cells to indicate a mucosal surface • Anti-epiligrin CP is associated with malignancy, especially adenocarcinomas (epiligrin is another name for laminin 5)Dermatitis Herpetiformis uTIP • DIF shows granular IgA in dermal papillae aClue is neutrophils clustered in dermal • Linear IgA disease (or chronic bullous disease of papillae adjacent to a subepidermal split childhood) can look histologically the same, but DIF shows linear IgA at the DEJ • Differential diagnosis includes bullous SLE, EBA, neutrophil-rich BP, cicatricial pemphigoidEpidermolysis Bullosa Acquisita (EBA) • Subepidermal separation • Can look histologically like BP or like DH (with neutrophils) or non-inflammatory • Salt-split skin differentiates EBA from BP • Antibodies to type VII collagen (290 kDa)Porphyria Cutanea Tarda (PCT) • Subepidermal blister with clean break • Minimal lymphocytic infiltrate, prominent solar elastosis, slightly eosinophilic necrotic keratinocytes, erythrocytes within blister • Festooning of dermal papillae • “Caterpillar bodies” → eosinophilic elongated, wavy structures in lower and midepidermis lying parallel to BM zone • DIF with IgG, IgM, IgA, C3 at DEJ and around vessels • Pseudoporphyria can look histologically exactly like PCT5.8 CYSTSApocrine Hidrocystoma • The cyst lining shows apocrine-type decapitation secretion • Fibrous pseudocapsule • Lined by a double layer of epithelial cells: outer flattened vacuolated myoepithelial cells, and inner tall columnar cells • Unilocular or multilocular Figure 5-26. Apocrine Hidrocystoma Dermatopathology  169
  • 18. Branchial Cyst • Most common site is along the side of the neck • The cyst lining is stratified squamous or pseudo-stratified columnar with cilia • Prominent lymphoid follicles deep to the wallBronchogenic Cyst • Majority present on precordium or suprasternal • In dermis or subcutis, epithelial lining thrown into folds → pseudostratified cuboidal or columnar and ciliated with mucus secreting goblet cells, which distinguish this cyst from othersCutaneous Ciliated Cyst • Majority present on the thighs of women • Epithelial lining is cuboidal or columnar with cilia on the surface and collagen/vessels deep to the wallDermoid Cyst • Most common site is the lateral eyebrow area • The epithelial lining is stratified squamous with adnexal structures (hair follicles, sebaceous glands, eccrine/apocrine glands)Epidermoid Cyst (Infundibular Cyst) • Punctum usually present, unilocular and spherical, lined by epidermis-like epithelium with a granular layer • Rupture associated with a foreign body granulomatous reactionMedian Raphe Cyst • Majority present on the ventral penis; sometimes ventral scrotum or perineum • Epithelial lining pseudostratified columnar +/- mucinous cellsPilar (Trichilemmal) Cyst • Fibrous capsule surrounding layer of dark-staining basal cells • Keratinization without granular layer, most superficial cyst cells are larger with more abundant cytoplasm • Cholesterol clefts seen in most lesions, and some show calcificationSteatocystoma • The keratin inside the cyst can resemble the keratin of an epidermal inclusion cyst, but the lining of the cyst is more corrugated with a bright pink ribbon- like surface; sebaceous glands are seen connecting to or adjacent to the wall • Multiple steatocysts associated with pachyonychia congenita type II (Jackson- Lawler) Figure 5-27. Steatocystoma170  2011/2012 Dermatology In-Review l Committed to Your Future
  • 19. Thyroglossal Duct Cyst • Cyst lining is stratified squamous or pseudostratified cuboidal/columnar +/- cilia • Deep to the wall are mucous glands, thyroid follicles, lymphocytic infiltrateVellus Hair Cysts • Mid-dermal cyst with follicular lining, containing laminated keratin and many vellus hairs • Occasionally in continuity with epidermis, telogen follicle, or a pilomotor muscle5.9 DEPOSITION DISORDERS Figure 5-28. Vellus Hair CystsCalcinosis Cutis • Chunky dark blue material in the dermis • May be idiopathic, dystrophic, or metastaticColloid Milium • Deposits generally larger (can extend from the papillary dermis into the reticular) than in macular or lichen amyloidosus, with a cracked/clefted appearance • There may be solar elastosis • Juvenile colloid milium is histochemically indistinguishable from amyloid derived from keratinFocal Cutaneous Mucinosis Figure 5-29. Calcinosis Cutis • Papule or polypoid (unlike pretibial myxedema) • Location shows no thickened stratum corneum • Lesion located in mid and upper dermisFollicular Mucinosis (Alopecia Mucinosis) • Mucinous degeneration of the external root sheath and sebaceous glands, accompanied by variable inflammatory infiltrate • Mucin in the follicle • Follicular infundibulum shows vacuolar alteration • If associated with mycosis fungoides, may show atypical lymphocytes and Pautrier microabscesses • Mucin stains positive with alcian blue; perifollicular scarring can be a feature Dermatopathology  171
  • 20. Macular and Lichen Amyloidosus • Lichen amyloidosus has a hyperplastic epidermis compared to the macular form • Both conditions have pink globs of material within the papillary dermis high up against the rete •  Associated with MEN IIaMucocele • On mucous membranes • If intact it can look like a subepidermal vesicle • Often ruptured, so there is light blue material with numerous inflammatory cells and muciphages and granulation Figure 5-30. Macular and Lichen Amyloidosus tissue • Clue is the presence of salivary glandsMyxoid Cyst • Not a true cyst; devoid of lining • Consists of large pool of mucin containing spindle/stellate fibroblasts • Compressed collagen at the periphery • Overlying epithelium is atrophic and hyperkeratotic • Look for acral location • Pool of mucin with spindle cells, often with an epidermal collaretteNodular Amyloid • Deposits of amyloid in papillary and reticular dermis and may involve subcutaneous fat • Plasma cells around blood vessels at margin of amyloid deposits • Amyloid deposits may thicken blood vessel walls • Colloid milium is more focal and involves only the upper dermisOsteoma Cutis • Within the dermis, well-circumscribed nodule of mature lamellar bone, often containing narrow spaces • No ghost cells seen, so don’t confuse with ossified pilomatricomaPapular Mucinosis (lichen myxedematosus) • Collagen fibers widely separated by mucin deposits, increased numbers of fibroblasts • Epidermis may be normal, acanthotic, or atrophic • In scleromyxedema variant, fibroblasts are numerous (increased in number) with consequent fibrosis (increased collagen) and thickening of dermis with mucin • More cellular than pretibial myxedemaPretibial Myxedema • Epidermis often hyperkeratotic with follicular plugging • Dermis shows separation of collagen bundles by large quantities of mucin172  2011/2012 Dermatology In-Review l Committed to Your Future
  • 21. • Stellate fibroblasts are evident; relatively acellular and non-inflammatory • No increase in fibroblasts • Square biopsy • Associated with Grave’s disease and thyroid acropachyScleredema • Reticular dermis greatly thickened, often with loss of subcutaneous fat • Eccrine trapping, broadened collagen fibers • Mucin demonstrated by Alcian blue or colloidal iron stain • Associated with diabetes, streptococcal infection, paraproteinemiaScleromyxedema • Fibroblasts are greatly increased with consequent fibrosis (increased collagen) and thickening of dermis • Mucin is increased • More cellular than pretibial myxedema • Associated with paraproteinemia, generally IgG lambda • Square biopsy5.10 DRUG REACTIONSFixed Drug Eruption • Basketweave stratum corneum • Interface dermatitis • Necrotic epidermis with possible subepidermal blister • Civatte bodies • Superficial and deep lymphohistiocytic infiltrate with scattered eosinophils and neutrophils (before you choose EM, check for eos) • Pigment incontinence with melanophagesu TIP Figure 5-31. Fixed Drug Eruptiona  emember: PLEVA has parakeratosis and lacks R the eosinophils u TIPLichenoid Drug a 3  types: blue-black in scars on the • Band-like lichenoid infiltrate at the DE junction face, blue-gray on legs, muddy-brown on sun-exposed areas; first 2 may be • Basal cell hydropic degeneration at the basal layer of the secondary to a drug metabolite-protein epidermis complex • Presence of eosinophils and parakeratosisMinocycline-induced Pigmentation • The blue-black color in scars on the face stains like hemosiderin (Perls-positive) • Blue-gray on legs stains like iron and melanin (stains with Perls and Fontana Masson) • Muddy-brown color on sun-exposed areas shows increased basal melanization and melanophages (probably secondary to phototoxicity) Dermatopathology  173
  • 22. Neutrophilic Eccrine Hidradenitis • Most commonly secondary to chemotherapy, especially cytarabine • On biopsy there is a dense neutrophilic infiltrate around the eccrine glands5.11 FAT DISORDERSAlpha-1-Antitrypsin Deficiency Panniculitis • Lobular panniculitis • Focal inflammation with large numbers of neutrophils that pour into the dermis • Fat necrosis is common • Loss of elastic tissue on special staining, no vasculitis • Lipid-laden foamy macrophages sometimes evidentAngiolipoma • A lipoma with blood vessels • Usually encapsulated, mature adipocytes admixed with anastomosing small blood vessels • Luminal microthrombi always presentErythema Induratum (Nodular Vasculitis) • “Messy-looking,” diffuse process • Nodular granulomatous panniculitis, predominantly lobular with spill over into the fibrous septa • Fat necrosis, with dense neutrophilic infiltrate • Infiltrate consists of neutrophils, lymphocytes, histiocytes, epithelioid cells and giant cells, lipid-laden foamy histiocytes • Vasculitis (often at dermal/SC junction) with endothelial swellingErythema Nodosum • Septal panniculitis, with widened fibrous septa • Lymphohistiocytic infiltrate with multinucleated giant cells (Touton giant cells), scattered eosinophils • No evidence of either vasculitis or necrosis • Sparse lymphohistiocytic infiltrate also around blood vessels in dermisHibernoma • Deep benign tumor, resembles normal brown fat • “Ping pong balls” stuffed into cells Figure 5-32. Erythema Nodosum → admixture of mature univacuolated adipocytes and multivacuolated large adipocytes with central nuclei and granular eosinophilic cytoplasm • Highly vascularized septa; don’t mistake for a granular cell tumor • “Mulberry cells” with scalloped nuclei secondary to vacuoles (cells have increased mitochondria)174  2011/2012 Dermatology In-Review l Committed to Your Future
  • 23. Lipodermatosclerosis (LipomembranousPanniculitis) • Lobular panniculitis • Fatty cysts lined by eosinophilic hyaline membranes that present a “ragged border” → lipomembranous change • Superimposed venous stasis changes in the dermisLupus Profundus • Overlying epithelium and superficial dermis may show features of DLE, or be unaffected • Within deep dermis and extending into widened septae of subcutaneous fat is a Figure 5-33. Lupus Profundus dense chronic inflammatory cell infiltrate of plasma cells and lymphocytes • Hyaline necrosis of fat with a mostly lobular panniculitis • Lymphoid follicles sometimes presentPancreatic Panniculitis • Lobular panniculitis, fat necrosis with “ghost cells” having no nuclei • Adipocytes contain granular eosinophilic or basophilic (calcified) debris • Neutrophil infiltrate around foci of fat necrosis, hemorrhage, uninvolved surrounding fat is heavily infiltrated by inflammatory cells, some of which are foamy due to ingested lipid, often there are multinucleated giant cellsPolyarteritis Nodosa • Septal panniculitis with medium-sized vessel vasculitis • Inflammation tightly localized around vessel • More fibrinous change and thus REDDER than thrombophlebitisSubcutaneous Fat Necrosis of the Newborn • Intense necrosis • Adipocytes swollen and contain radially arranged eosinophilic crystalline crystals • Heavy inflammatory cell infiltrate including foreign body giant cells • Older lesions may show calcification and fibrosis • Similar findings in post-steroid panniculitis5.12 FIBROUS/FIBROHISTIOCYCTIC DISORDERSAcrochordon • Normal or hyperplastic epidermis surrounding a core of fibrovascular tissue with loose or dense collagen fibers • Absence of adnexal structures • Fat cells may be present → nevus lipomatosus superficialis Dermatopathology  175
  • 24. Acquired Digital Fibrokeratoma • Acral location • Pedunculated and covered by variably acanthotic and hyperkeratotic skin • Core composed of dense collagen fibers oriented in the direction of the vertical axis of the lesion • No nerve bundles and no koilocytesAngiofibroma (Fibrous Papule of the Face,Pearly Penile Papules, Koenen’s Tumor) • Fibrosis, sometimes in an “onion-skin” pattern around vessels • Scattered stellate fibroblasts and increased vascularity Figure 5-34. Acquired Digital Fibrokeratoma • Localized area of fibroplasia and vascular proliferation in the upper dermis • Hypocellular • Fibrous banding around follicles • Stains positive for factor XIIIa • Multiple lesions seen in tuberous sclerosis and MEN IAtrophie Blanche (Segmental HyalinizingVasculitis) • Increased number of dermal vessels containing fibrinoid plugs • Thick red walls of the vessels • Frank vasculitis is not a feature • Variable degree of purpura with Figure 5-35. Angiofibroma hemosiderin pigment • In fully established plaques there is epidermal atrophy with scleroderma-like scarringAtypical Fibroxanthoma • Well-defined, dermal lesion • Often, epidermal collarette; the deep margin pushes rather than invades • High-grade atypia; composed of a pleiomorphic mix of spindle cells, histiocyte-like cells, atypical xanthomatous cells (classically seen), and multinucleated giant cells • Mitotic activity and hyperchromasia can be present Figure 5-36. Atypical Fibroxanthoma176  2011/2012 Dermatology In-Review l Committed to Your Future
  • 25. • Stains positive for CD68, alpha-1 antitrypsin, muscle-specific actin, CD10, CD99 u TIP aMake sure there isn’t an overt malignant melanoma in situ or SCC at epidermisDermatofibroma (Fibrous Histiocytoma,DF) • Interlacing fascicles of slender spindle cells (running haphazardly) • Often storiform, within a loose collagenous or myxoid stroma, scattered foamy histiocytes, multinucleated giant cells Figure 5-37. Dermatofibroma (Fibrous Histiocytoma) • Periphery of lesion shows hyaline collagen bundles surrounded by tumor cells, grenz zone seen; don’t count on pigmented epidermal hyperplasia • Multiple DFs seen in lupus erythematosus and immunosuppression/HIV • Factor XIIIa-positive and stromelysin-3  positive u TIP aNot well-circumscribed on low power (don’t go to high power)Dermatofibrosarcoma Protuberans (DFSP) • Dermal tumor, more cellular than DF Figure 5-38. Dermatofibrosarcoma Protuberans with smaller cells, irregular infiltration of subcutaneous fat • Uniform spindle cells with elongated nuclei showing little or no pleiomorphism • Storiform pattern with whorls; there is a myxoid variant • CD34-positive • Giant cell fibroblastoma is also CD34-positive, and is usually seen in male children on the neck/trunk → thought to be a juvenile counterpart of DFSP • Translocation t(17;22)(q22;q13) has been demonstrated; this translocation results in the fusion of two genes: collagen type I alpha 1(COL1A1) and platelet-derived growth factor B-chain (PDGFB)Epithelioid Sarcoma • Forearms of young adults • Epithelioid cells mixed with spindle cells with granulomatous inflammation in fibrotic stroma with necrosis (can look like a palisading granulomatous disorder), atypia, mitoses, and vascular invasion Dermatopathology  177
  • 26. • Must rule out infectious causes (therefore, unlikely you would make this diagnosis on the Boards without clinical history) • Vimentin+, low molecular weight cytokeratin+Giant Cell Epulis • Exact counterpart of the giant cell tumor of tendon sheath but more superficial and with mucous membrane epitheliumGiant Cell Tumor of Tendon Sheath • Deep tumor; lobulated and well-defined, often with a fibrous pseudocapsule • Xanthomatous cells, siderophages, and conspicuous giant cells (osteoclastic giant cells → purple and angulated) • Prominent collagenous stroma, mitotic figures may be numerous, CD68 positive stainingInfantile Digital Fibromatosis • Irregular mass of proliferating spindle-shaped myofibroblasts embedded in a dense collagenous stroma extending deeply from the dermis • Finding brightly eosinophilic, PAS+, pink circular intracytoplasmic inclusions in the myofibroblasts is diagnostic → thought to be aggregates of actinKeloid • Nodular fibroblastic proliferation and the presence of hypocellular, glassy, eosinophilic, hyalinized and disordered collagen fibers in dermis • Rubinstein-Taybi, Noonan’s, and Turner’s syndromes can have multiple keloidsNodular Fasciitis • Clinically presents as a rapidly-growing Figure 5-39. Keloid tumor in a younger person • Unencapsulated, deep mass of plump spindle cells set in a loose myxoid and collagenous stroma • Thin-walled blood vessels, ramify through lesion in a radial arrangement; foci of extravasated RBC’s • Mitotic cells but without atypia • More heterogeneous than a DFSP • Immunohistochemistry positive for muscle actin, but desmin is negativeHypertrophic Scar • Nonspecific dermal fibroblastic proliferation, often with epidermal atrophy Figure 5-40. Nodular Fascilitis178  2011/2012 Dermatology In-Review l Committed to Your Future
  • 27. • More cellular than keloids • Hyalinized collagen fibers less prominent; fascicles and bundles seenScar • Spindle-shaped cells intermixed with varying amounts of collagen (dependent on the age of the scar) with vessels oriented perpendicularly to the epidermis • Lack of adnexae5.13 GENODERMATOSESBirt-Hogg-Dube • Triad of fibrofolliculomas, skin tags, and trichodiscomas • Increased risk of renal cancer and spontaneous pneumothorax • Autosomal dominant, molecular defect in folliculinCowden’s Disease • Multiple trichilemmomas, sclerotic fibromas (storiform collagenoma), acral keratoses, oral fibromas • Increased risk of breast/thyroid cancer • Autosomal dominant, mutation in PTEN  geneEpidermolytic Hyperkeratosis (BullousCongenital Ichthyosiform Erythroderma) • Hypergranulosis • Prominent vacuolization of the superficial Figure 5-41. Cowden’s Disease epidermal cells • Stippled keratohyaline granules; higher up there is “drop out” of nuclei • Seen in bullous CIE, benign keratoses, epidermal nevi, or incidental • Autosomal dominant, defect in keratins 1/10Ichthyosis Vulgaris • Orthokeratosis with hypogranulosis/absent granular layer • Autosomal dominant, defect in filaggrin/profilaggrinIncontinentia Pigmenti • Eosinophilic spongiosis with dyskeratotic cells • Pigment incontinence with melanophages in dermis in later stages • Verrucous lesions show hyperkeratosis, acanthosis, papillomatosis and focal dyskeratosis • X-linked dominant, mutation in NEMO gene Dermatopathology  179
  • 28. Porokeratosis • Keratin-filled epidermal invagination with an angulated parakeratotic tier, the cornoid lamella • Epithelium deep to tier is devoid of granular cell layer, adjacent epithelium toward lesion’s center is often atrophic • Always look to periphery of a lichenoid infiltrate to check for the cornoid lamellaPseudoxanthoma Elasticum • Degenerative changes of elastic fibers of middle and lower dermis • Elastic fibers readily identifiable on H&E, appearing “pink and squiggly” → widely dispersed granular material amidst Figure 5-42. Porokeratosis normal collagen fibers • Elastic fibers stain positive with von Kossa stain • Transepidermal elimination of degenerate elastic tissue may be seen; calcification seen in older lesions • Autosomal recessive or dominant5.14 GRANULOMATOUS DISORDERSLeprosy, Borderline • Multiple nodules consisting of epithelioid tubercles in the superficial and deep dermis • Nodules are not rounded, but more irregular and elliptical • The infiltrate within these nodules is lymphohistiocytic • Infiltrate found around nerve bundlesLeprosy, Lepromatous • Histiocytes in poorly circumscribed masses in the dermis with few, if any, lymphocytes • Histiocytes are often foamy (dermis shows lots of pallor), and distended (termed virchow cells) with large groups (globi) of leprosy bacilli (revealed by Ziehl-Neelsen or Fite stain) • Grenz zone seen → may destroy cutaneous appendages and extend into subcutaneous fatLeprosy, Tuberculoid • Epithelioid non-caseating granulomatous response around small cutaneous nerves • Often extending into adjacent dermis • Langerhans giant cells, scarce bacilliLichen Nitidus • Atrophic epidermis covered by a parakeratotic tier • Interface dermatitis • Claw-like extension of the epidermal ridges mark lateral boundaries of an lymphohistiocytic infiltrate (“ball and claw”) • Giant cells and granulomata may be seen180  2011/2012 Dermatology In-Review l Committed to Your Future
  • 29. Sarcoidosis • Fairly normal epidermis • “Naked,” noncaseating epithelioid tubercles (sparse lymphocytic infiltrate) located throughout the mid and deep dermis • Diagnosis of exclusion; can be identical to foreign body reaction (silica, beryllium, etc.) and granulomatous rosacea •  chaumann body (basophilic, rounded S structure composed of calcium carbon- ate, phosphate, and iron) and asteroid body (lipoprotein, eosinophilic, star- shaped), neither body is specific for sar- Figure 5-43. Lichen Nitidus coid (seen also in TB, leprosy, berylliosis)5.15 HISTIOCYTOSESJuvenile Xanthogranuloma • Intradermal collection of uniform lipid-laden histiocytes, admixed with multinucleated giant cells of Touton and foreign body types (but Touton giant cells not specific for JXG, and can be seen in any xanthomatous process) • Variable numbers of neutrophils, eosinophils, mast cells, and lymphocytes, no epidermal involvement • Multiple JXGs are associated with ocular involvement; even 1 JXG associated with neurofibromatosis and CML Figure 5-44. SarcoidosisLangerhans Cell Histiocytosis • Infiltrate in upper dermis → uniform cells with pale reniform vesicular nuclei and pale-staining or eosinophilic cytoplasm • An edematous zone of “floating cells” in the upper dermis → each cell seen individually • Epidermotropism is characteristic as are Pautrier microabscesses; scattered eosinophils • Birbeck granules • S100 and CD1a positive; langerin (CD207)  positive (most specific) Figure 5-45. Juvenile Xanthogranuloma Dermatopathology  181
  • 30. Reticulohistiocytosis •  ulticentric type seen more often in older women, associated with arthritis mutilans, often M seen clustered around the nail → “coral bead sign,” associated with breast cancer • Well-defined collection of uniform pink histiocytes and multinucleated giant cells with “ground glass” (not foamy) cytoplasm → located predominantly in dermisVerruciform Xanthoma • Clinically often on oral mucosae or genital area • Regular acanthosis, parakeratosis, and hyperkeratosis • Bulbous epidermal ridges penetrate to same depth, giving level lower border, expanded ridges with marked central keratinocyte necrosis and heavy neutrophil infiltrate • Papillary dermis between elongated epidermal ridges contains large numbers of eosinophilic foamy xanthoma cells, but no Touton cells present5.16 INFECTIONSActinomycosis • Contains sulfur granule (organism tangled together in matted colony) with an eosinophic rim – Splendore-Hoeppli phenomenon – with dense surrounding neutrophilic infiltrateBlastomycosis • Pseudoepitheliomatous hyperplasia overlying abscesses • Organisms (8-15 microns) with broad- based buddingChromoblastomycosis • Pseudoepitheliomatous hyperplasia overlying abscesses with presence of Figure 5-46. Actinomycosis “copper pennies” = sclerotic bodies = medlar bodies = hot cross buns (6-12 microns)Coccidioidomycosis • Spherules (which contain and can collapse to release endospores → 10-80 microns) • Combination of suppuration with pseudoepitheliomatous hyperplasia • Rhinosporidiosis sporangium is biggerCondyloma Acuminatum • Marked acanthosis, papillomatosis, with hyperkeratosis and parakeratosis Figure 5-47. Chromoblastomycosis182  2011/2012 Dermatology In-Review l Committed to Your Future
  • 31. • Sharp margination, superficial vacuolated keratinocytes (koilocytes)Cryptococcosis • Spherical yeast, narrow-based single budding • Mucinous capsule showing gelatinous clearing • May be a granulomatous pattern that has rare organisms •  ucicarmine positivity of capsule dis- M criminates between cryptococcus and other tissue fungal infections such as his- toplasmosis and blastomycosis • Gelatinous pattern shows numerous Figure 5-48. Condyloma Acuminatum vacuolated-like areas containing abundant encapsulated organisms 4-20 microns (larger than histoplasmosis)Epidermodysplasia Verruciformis • Bluish change in the granular layer (thought to be ribosomes) • Associated with HPV types 5, 8 • Associated with immunosuppression/HIV in sporadic form and is also inherited in an autosomal recessive form • Mutations have been found in the EVER1 and EVER2 genes; these genes are on 17q25, the location of the PSORS2 gene (one of the genes implicated in the inheritance of psoriasis) Figure 5-49. CryptococcosisHerpes Simplex Virus Infection • Suprabasilar intraepidermal bullae (ballooning) • Mixed cell infiltrate consisting of neutrophils and eosinophils • Multinucleated giant cells with marginated chromatin, steel-gray nuclei, reticular degeneration with strands of cytoplasm • May have subepidermal bullae; can look identical to erythema multiforme in the lateral aspects of lesion • May see Cowdry A bodies (Lipschutz bodies) Figure 5-50. Herpes Simplex Virus Infection Dermatopathology  183
  • 32. Histoplasmosis • Not encapsulated; 2-4 microns yeast within distended macrophages as a basophilic dot with surrounding artefactual halo (pseudocapsule) • Similar to Leishmania, but lacking in the kinetoplast • Stains positive with PAS and methenamine silverLeishmaniasis • Amastigotes (little dots) within macrophages (Leishman-Donovan bodies), 2-4 microns, kinetoplast present Figure 5-51. Histoplasmosis • Acanthotic epithelium, with frequently ulceration • Epidermis may show pseudoepithelio- matous hyperplasia and intraepidermal neutrophilic abscesses, dermis contains intense infiltrate of histiocytes, lympho- cytes, and plasma cells • Organisms best seen with Giemsa stain • Looks like histoplasmosis, but histoplasmosis has a tiny “halo” around the organismMolluscum Contagiosum • Lobulated, endophytic hyperplasia • Keratinocytes contain very large intracytoplasmic inclusions, that Figure 5-52. Leishmaniasis compress the nucleus against the cell membrane (Henderson-Patterson bodies) → fill the cells in a cup-shaped invagination of the epidermis, often at the hair follicleOrf (Ecthyma Contagiosum) • Acral skin; symmetric nodule • Parakeratosis and acanthosis; early lesion shows intracytoplasmic eosinophilic inclusion bodies in the upper 1/3 of the epidermis • Ballooning without multinucleated cells • Epidermis can be hyperplastic with down-growing rete, dermal inflammation and vasodilation of vessels • May show necrosis; cowpox is identicalProtothecosis • Caused by an algae, most commonly Prototheca wickerhamii • Organism looks like a soccer ball on histopathology (6-10 mm) → the morula184  2011/2012 Dermatology In-Review l Committed to Your Future
  • 33. Scabies • Burrow within horny layer, with only blind end (with female mite) located in stratum malpighii • Spongiosis in stratum malpighii near mite • Dermal infiltrate of eosinophils and lymphocytes in lesions containing mites • Occasionally scybala (feces) can be seenSyphilis, Primary Chancre • Epidermal hyperplasia with intense lymphohistiocytic and neutrophil infiltrate in dermis • Plasma cells present • Overlying epidermis ulcerated, with adjacent epidermis showing pseudoepiltheliomatous hyperplasiaSyphilis, Secondary • Papular lesions show superficial and deep perivascular infiltrates that may become band-like; plasma cells (which are often deep) and histiocytes (pale infiltrate) • Parakeratosis, acanthosis, spongiosis, and exocytosis • Thick-walled blood vessels with swollen enthothelial cells characteristic • Psoriasiform syphilides show parakeratosis and acanthosis with extended epidermal ridges • Spirochetes can be seen in lower epidermis and in blood vessels Figure 5-53. Syphilis, Secondaryu TIPaExtravasated RBCs may be a feature of both papular and papulosquamous vari- ants; most commonly the infiltrate will be lichenoid → if you see lichenoid pattern, look for plasma cellsTinea Versicolor • Minimal spongiosis; organisms easily seen on H&E (unlike dermatophyte) in stratum corneum as spaghetti and meatballs (must see both)u TIPaThink of this diagnosis when skin appears normal or mildly inflamedVerruca Plana • Relatively flat lesion with the cells of the granular layer appearing to be clearer than usual (vacuolized) Figure 5-54. Verruca Plana Dermatopathology  185
  • 34. Verruca Vulgaris • Hyperkeratosis, papillomatosis, tiers of parakeratosis over tips of exophytic component • Prominent granular cell layer within which are vacuolated cells containing enlarged clumps of irregular keratohyalin granules (“owl’s eyes” or koilocytes) (seen in upper 1/3 of epidermis) • Dilated blood vessels in the dermal papilla5.17 INFLAMMATORYAcne Keloidalis • Early: Dilated follicle may contain pus extending through epithelium, surrounded by neutrophils, lymphocytes, and perhaps plasma cells • Later: Marked fibrosis/scarring, free broken hair shafts with foreign body giant cell reaction; possible lateral lymphoplasmacytic infiltrate • Identical findings in hidradenitis suppurativa, but this condition also likely shows sinus tracts lined by stratified squamous epithelium and surrounded by fibrosis and inflammationChronic Radiodermatitis • Hyperkeratosis, foci of parakeratosis, acanthosis or atrophy with flattened rete ridges • Spongiosis or basal cell liquefaction degeneration • Dermis is fibrotic, pale and sickly, and lacks inflammation (not square and red like morphea) • Bizarre (radiation) fibroblasts, thickened blood vessels with fibrointimal hyperplasia, or telangiectasia • Loss of appendagesCryoglobulinemia • Vascular dilatation, endothelial swelling, and plugging of vascular lumina by hyaline material (microthrombi) → red deposits • Same pattern for DIC, cryoglobulinemia, lupus anticoagulant, protein S and C deficiency, antithrombin III deficiency, coumadin and heparin necrosis, PNHLichen Planus-like Keratosis (Benign Lichenoid Keratosis) • Hyperkeratosis, hypergranulosis, variable u TIP acanthosis, and basal cell liquefaction aBig clue → hyperpigmentation of the basal layer; degeneration (worse than LP) no dysplasia like a lichenoid actinic keratosis • Parakeratosis commonly present (unlike LP) • Broadened, widened and irregular epidermal ridges (rather than sawtooth), dense band- like lymphohisticytic infiltrate in superficial dermis that may contain eosinophils and plasma cells; seen near lentigo or seborrheic keratosesErythema Annulare Centrifugum (Gyrate Erythema) • Well-demarcated perivascular infiltrate of lymphocytes and histiocytes → cuffing, but not always like this • Epidermis usually normal, but focal spongiosis can be seen • Make sure that there is no interface dermatitis of lupus, no papillary dermal edema of PMLEErythema Elevatum Diutinum • Leukocytoclastic vasculitis • Epidermis may show acanthosis and parakeratosis186  2011/2012 Dermatology In-Review l Committed to Your Future
  • 35. • Fibrinoid necrosis and neutrophil infiltration of vessels • Older lesions show granulomatous tissue and fibrous scarringErythema Multiforme • Subepidermal blister, with necrotic keratinocytes at all levels of epidermis • Vacuolar interface change • Basket weave stratum corneum (PLEVA doesn’t show this) • Lymphohistiocytic infiltrate especially at DE junction • Usually no eosinophils (but not a hard- Figure 5-55. Erythema Multiforme and-fast rule) • Infiltrate can be deepGranuloma Faciale • Dense, often nodular infiltrate in mid dermis • Grenz zone; involves both epidermis and hair follicles • Infiltrate involves eosinophils, neutrophils, plasma cells, mast cells, and lymphocytes, extravasated RBCs • Dilated blood vessels with fibrin deposition in their wallsGraft Versus Host Disease (GVHD) Figure 5-56. Granuloma Faciale • Acute disease shows widespread basal cell hydropic degeneration with scattered necrotic keratinocytes that are found in adnexae • Lymphocytic exocytosis with satellite cell necrosis (not always present) • Dermal edema with dilated blood vessels • Pigmentary incontinenceLeukocytoclastic Vasculitis • Subepidermal or intraepidermal blister with neutrophils, necrotic keratinocytes, basketweave stratum corneum • Edema of papillary dermis, with collection of neutrophils and nuclear dust around and obliteration of vessels • Fibrinoid degeneration of vessels, fibrin “blends into” surrounding collagen • Extravasated RBC’sLichen Simplex Chronicus • Psoriasiform hyperplasia with orthokeratosis, prominent granular layer, focal parakeratosis • Vertically oriented collagen fibers in elongated dermal papillae Dermatopathology  187
  • 36. • Superficial perivascular lymphohistiocytic infiltrate • Differential diagnosis includes hypertrophic LP, which shows a lichenoid infiltrateLichen Planus • Prototypical lichenoid inflammatory condition with a band-like infiltrate of lymphocytes sometimes obscuring the DEJ, with hyperkeratosis, wedge-shaped areas of hypergranulosis, irregular acanthosis, saw-toothing of the basal layer with squamotization of basal cells • Colloid/Civatte bodies Figure 5-57. Lichen Planus • Parakeratosis and eosinophils should be absent • LP on mucosa: Plasma cells without hypergranulosis (often on the Boards)Lichen Sclerosus et Atrophicus • Often, epidermal atrophy with confluent orthokeratosis, follicular plugging • Subepidermal bulla containing RBC’s • Superficial perivascular and band-like lymphohistiocytic infiltrate under a pale and sclerotic zone • Telangiectases in papillary dermis, homogeneous collagen in upper dermis, dermal edema Figure 5-58. Lichen Sclerosus et Atrophicus • Same as balanitis xerotica obliterans (BXO) • Patients may have circulatory autoantibodies to ECM-1Lichen Striatus • Mild parakeratosis, spongiosis; superficial perivascular inflammatory infiltrate of predominantly lymphocytes (rare plasma cells or eosinophils) that may be almost band-like superficially • Low power shows a nearly empty dermis, but deep dermis shows a dense infiltrate around the adnexal structures → very unique to this entity Figure 5-59. Lichen Striatus188  2011/2012 Dermatology In-Review l Committed to Your Future
  • 37. Lupus Erythematosus • Follicular plugging, mild hyperkeratosis, vacuolar change of basal layer, basement membrane thickening, pigment incontinence, increased dermal mucin • Superficial and deep perivascular infiltrate of lymphocytes and histiocytes that is periadnexal as wellMorphea • Square biopsy that is very red • Papillary dermis unaffected usually • Reticular dermis has swollen collagen bundles that are intensely eosinophilic and oriented parallel to surface, also septa of subcutaneous fat involved with atrophy of adipocytes and fibrosis, follicles and sebaceous glands are atrophic or absent • Eccrine trapping, dense, chronic inflammatory cell infiltrate of lymphocytes and plasma cells, mucin is not a large feature; there are no giant cellsPerforating Folliculitis • Widely dilated hair follicle containing ortho- and parakeratotic keratin, basophilic necrotic debris • Connective tissue elements and inflammatory cells • A curled up hair sometimes is found within the keratinous plugPerniosis • Acral location, with interface dermatitis, occasionally • Papillary dermal edema; infiltrate is diffuse and deep • Similar to PMLEPigmented Purpuric Dermatosis • Chronic capillaritis; superficial vessels dilated with endothelial cell hypertrophy and surrounding extravasated red blood cells • Perivascular lymphocytic infiltrate (no eosinophils or neutrophils) that may look lichenoid • Purpura in early lesions, and hemosiderin- laden macrophages (siderophages) seen in older lesions; pigment is deep (stain with Perls Prussian blue)u TIPaVariants include: progressive pigmentary dermsis of Figure 5-60. Pigmented Purpuric Dermatosis Schamberg, lichen aureus (clinically usually asymmetrical), eczematid-like purpura of Doucas and Kapetenakis, lichenoid dermatitis of Gougerot and Blum, purpura annularis telangiectoides of Majocchi Dermatopathology  189
  • 38. Pityriasis Lichenoides et VarioliformisAcuta (PLEVA) • Parakeratosis, pallor of upper epidermis • Spongiosis and vacuolar alteration of the basal layer with some necrotic keratinocytes at different levels • Papillary dermal edema • Band-like interface infiltrate and deep infiltrate composed of mostly lymphocytes with exocytosis of lymphocytes • Extravasated RBC’s in upper dermis • Can look just like LyP but LyP has eosinophils and neutrophils and PLEVA doesn’t Figure 5-61. Pityriasis Lichenoides et Varioliformis Acuta • Erythema multiforme doesn’t show parakeratosisPityriasis Rosea • Mounds of parakeratosis over slight acanthosis, and slight spongiosis • Superficial perivascular infiltrate predominantly lymphocytes • Extravasated RBC’s in papillary dermis with extension into the epidermis • Papillary dermal edemaPityriasis Rubra Pilaris • Acanthosis with broad and short rete ridges with slight spongiosis • Thick suprapapillary plates, focal or Figure 5-62. Pityriasis Rosea confluent hypergranulosis (variable) • Alternating orthokeratosis and parakeratosis both vertically and horizontally • Dermis shows mild superficial perivascular lymphocytic infiltrate • Unique feature → conical hyperkeratotic follicular plug is far above the epidermisPolymorphous Light Eruption (PMLE) • Variable epidermal spongiosis • Dermal, perivascular lymphocytic cell infiltrate with marked papillary dermal edema Figure 5-63. Pityriasis Rubra Pilaris190  2011/2012 Dermatology In-Review l Committed to Your Future
  • 39. • May resemble SCLE, but infiltrate more commonly around blood vessels than pilosebaceous units, and no vacuolar interface changes • Infiltrate goes deeper than SCLEPsoriasis • Lengthened and multilayered parakeratosis with neutrophils (Munro’s microabscesses) • Pallor of the upper epidermis • Hypogranulosis • Regular acanthosis of epidermis • Spiraled dilated vessels under thinned suprapapillary plates Figure 5-64. Polymorphous Light Eruption • Early lesions may show spongiosisRosacea, Granulomatous • Perifollicular • Telangiectases and round epithelioid tubercles that may caseate in superficial dermis • Surrounding lymphocytesSweet’s • Dense nodular infiltrate, composed primarily of neutrophils, histiocytes, and some lymphocytes • May be primarily histiocytoid • Nuclear dust (leukocytoclasis) is marked, the papillary dermis is edematous Figure 5-65. Psoriasis • Focal degeneration of collagen, extravasated RBC’s • No vasculitic changes; dermal edema should also make you think of PMLE, which has lymphocytesStasis Dermatitis • Hyperkeratotic epidermis with areas of parakeratosis, acanthosis, and focal spongiosis • Superficial, perivascular lymphohistiocytic infiltrate that surrounds plump, thickened capillaries and venules • Superficial dermal vessels may be arranged in lobular aggregates • Reticular dermis is often fibrotic and hemosiderin is usually present deepToxic Epidermal Necrolysis • Confluent wipe-out of the epithelium, full-thickness necrosis, subepidermal vesiculation, sparse inflammation Dermatopathology  191
  • 40. 5.18 LYMPHOMAS AND MARKERSB-cell Lymphoma u TIP • Often a diffuse, deep infiltrate aThe 2005 WHO-EORTC and 2008 WHO Classification of • Germinal centers may be present primary cutaneous B-cell lymphomas has 4 main categories: follicle center lymphoma; marginal zone lymphoma; diffuse (especially in primary cutaneous follicle large B-cell lymphoma, leg type or other/NOS center lymphoma with a follicular growth pattern) • Often can be “bottom heavy” involving subcutaneous fat lobules • Epidermis generally spared • CD20+Leukemia Cutis • AMML is the most common (acute myelomonocytic leukemia; myeloid precursors); grenz zone present • Dense diffuse infiltrate in dermis and extending into subcutaneous fat; cells splayed out through the stroma → some Indian-filing; not always highly atypical, darkly staining small- to medium-sized cells • Infiltrate may be sparse or dense • Neoplastic cells stain positive for Leder, lysozyme, myeloperoxidaseLymphoma Cutis • Diffuse infiltrate • No germinal centers; infiltrate goes deep without a pattern • Often can be “bottom heavy” involving subcutaneous fat lobules • Epidermis spared • CD20+Lymphomatoid Papulosis (LyP) • PLEVA-like architecturally, but cells more atypical; infiltrate is wedged-shaped with base of wedge in close apposition to the epidermis • Early lesions may not affect epidermis, while in older lesions the infiltrate may be lichenoid; interface might be obscured by infiltrate • LyP has eosinophils and neutrophils intermixed with atypical lymphocytes that look like “chunks of coal” • Most cells are CD3 positive and CD4 positiveu TIPaType A: CD30-positive; pleomorphic cells are large with vesicular nuclei; Reed-Sternberg-like multinucleate giant cells; neutrophils, eosinophils, and plasma cells a ype B: MF type with preponderance of Sezary- T type cells aType C: like anaplastic large cell lymphoma aType D: like aggressive epidermotropic CD8+ cytotoxic T=cell lymphoma Figure 5-66. Lymphomatoid Papulosis192  2011/2012 Dermatology In-Review l Committed to Your Future
  • 41. Mantle Cell Lymphoma • Clinically: Most patients have disseminated disease at the outset, 1/3 have leukemic involvement; cutaneous lesions have been reported to precede internal disease • Characteristically bcl-1 (Cyclin D1) positive [t(11;14) translocation involving bcl-1 and the immunoglobulin heavy chain gene] • Also positive with CD 19, CD 20, CD5 (like CLL), CD43, bcl-2 • Lack CD 23 (unlike CLL) • Mantle cells have cell surface immunoglobulins (often IgM and IgD) • Often has lambda light chain restrictionMycosis Fungoides (MF) • For Board purposes, a slide of MF should have most of these criteria: – Larger intraepidermal lymphocytes compared with smaller dermal lymphocytes – Pautrier’s abscesses – Disproportionate exocytosis in relation to spongiosis – Basilar lymphocytes lined up against the DEJ (“toy soldiers," “strings of pearls”) – Pagetoid spread of lymphocytes into the epidermis Figure 5-67. Mycosis Fungoides – 7-9 micron convoluted lymphocytes (a basal keratinocyte is about 7-9 microns) – Halo’d lymphocytes in the epidermis – Papillary dermal fibrosis, so-called “fettucine” collagen – CD4+ cells in the epidermis that have often lost CD5 and CD7 • Note that type B lymphomatoid papulosis can look exactly like MF histologicallyPseudolymphoma (Reactive Lymphoid Hyperplasia) • Dense nodules consisting of small lymphocytes and histiocytes • Germinal center (centrocytes and centroblasts) morphology with surrounding mantle and then marginal zone, surrounding T-cells → nodules involve both the upper and lower dermis (more “top heavy”) • Lymphocytes, eosinophils, ectopic adipocytes • In center of reactive follicle are “tingible body macrophages”Subcutaneous Panniculitis-like T-cell Lymphoma • Clinically patients present with subcutaneous nodules on the extremities, can have a fatal hemophagocytic syndrome • Biopsy can be subtle; should see a septal and lobular panniculitis with medium to large atypical lymphocytes, rimming of fat cells with atypical lymphocytes, necrosis; there may be phagocytosis of lymphocytes/debris/erythrocytes Dermatopathology  193
  • 42. • Two groups: 1.) Alpha-beta T-cells (by definition) that are CD 8+, more indolent clinically 2.) Gamma-delta T-cells that are CD 56+, more aggressive (fatal) with systemic hemophagocytosis - this subset is now considered a subset of cutaneous gamma- delta T-cell lymphomas (a provisional diagnosis) u TIP Cell Markers w Markers •  CD1a – Langerhans cells •  CD2, CD3 – Pan T-cell •  CD4 – Helper T-cell – Also expressed by histiocytes (Langerhans cells) •  CD5 – Pan T-cell – Marker of CLL, mantle cell lymphoma – Lost in MF •  CD7 – T-cells – Lost in MF •  CD8 – Cytotoxic T-cell •  CD10 – Marker for primary cutaneous follicle center lymphomas •  CD16 – NK cell marker •  CD19, CD20, CD79a – B cell marker •  CD23 – Positive marker in CLL – Negative marker in Mantle cell lymphoma •  CD30 – Marker for anaplastic large cell lymphoma, lymphomatoid papulosis, Hodgkin’s, transformed MF •  CD45 (aka LCA=leukocyte common antigen) – T-cells, B-cells, myeloid cells, histiocytes •  CD56 – NK cell marker •  CD57 – T-cells with NK activity •  CD138 – Plasma cell marker, CD79a •  Bcl-1 – Marker for mantle cell lymphoma •  Bcl-2 – Anti-apoptotic – Marker for follicular cell lymphoma (nodal) – Primary cutaneous follicle center lymphomas are generally bcl-2 negative – Stains BCCs diffusely whereas stains only the outer rim of epithelium in trichoepitheliomas •  Bcl-6 – Marker for primary cutaneous follicle center lymphomas •  MUM-1/IRF4 – Marker for diffuse large B-cell lymphomas, leg type 194  2011/2012 Dermatology In-Review l Committed to Your Future
  • 43. Figure 5-68. Immunohistochemical Stains for the Diagnosis of Some Cutaneous Lymphomas5.19 MELANOCYTIC LESIONSAtypical Nevus (Dysplastic Nevus, Nevus with Architectural Disorder, Clark’s Nevus) • May be junctional or compound; in compound lesions, the epidermal component extends beyond the lateral border of the dermal nevus cells (shoulder phenomenon), little or no pagetoid spread, lentiginous melanocytic hyperplasia with elongation of rete ridges • Melanocytes have increased nuclear size, nuclear membrane irregularity, prominent nucleoli, and pleomorphism and are randomly distributed along basal layer; marked fixation artefact, fusion of adjacent nests, rare mitoses • Periepidermal fibroblastic response → lamellar fibroplasia; random atypia (not uniform)Balloon Cell Nevus • Round or oval cells with abundant pale-staining or clear cytoplasm • The cells contain a central hyperchromatic or vesicular nucleus with very conspicuous nucleolus • Looks like a xanthoma, but distinguish by looking high in dermis as cells may go into epidermis (compound or intradermal), contain melanin, or show nestingBlue Nevus, Cellular • Large, often well-circumscribed, nodular mass that fills the dermis and may penetrate into subcutaneous fat • Gets more cellular as you look lower in dermis Dermatopathology  195
  • 44. • Composed of a dual cell population: large numbers of closely aggregated large spindle and epithelioid cells admixed with heavily pigmented cells • Melanophages • Tumor cells may be divided into nests and cords by collagenous septae, no atypia and rarely mitotic figures present • Very rarely, melanoma may develop withinBlue Nevus, Common • Typically in upper dermis, heavily pigmented dendritic spindle cells with associated host-derived dense fibroblastic and collagenous spindle cell response • Often associated heavily pigmented melanophages • No mitotic figures and no pleomorphism • Overlying epidemis is normal • Completely benign lesionBlue Nevus, Combined • Association of a common blue nevus with an overlying melanocytic nevus Figure 5-69. Blue Nevus, CommonNevus, Congenital • Frequently hyperkeratosis, acanthosis, and papillomatosis • Neonatal lesions are compound and develop within acanthosis • Melanocytes may present as well- circumscribed nests or as single cells scattered through all layers of epidermis • Nevus usually is a diffuse infiltrate of melanocytes from papillary dermis into deep reticular dermis and possibly subcutaneous fat • Nevus cells ensheath epidermal appendages and can be found within arrector pili muscles, hair follicles, Figure 5-70. Blue Nevus, Combined sebaceous glands and the walls of eccrine sweat ducts • With increasing depth the nevus cells adopt a single-cell array and Indian-file patternDeep Penetrating Nevus • May be a variant of blue nevus or congenital nevus • Symmetrical, wedge-shaped, conglomerate of spindle and epithelioid cells that extend into deep reticular dermis/fat • No upward extension of melanocytes (Pagetoid spread) • Often surrounds follicles/nerves/glands196  2011/2012 Dermatology In-Review l Committed to Your Future
  • 45. Halo Nevus • Raised dermal nodule, acanthotic and frequently hyperkeratotic epidermis • Nevus is usually compound and infiltrated extensively by lymphocytes and histiocytes with occasional mast and plasma cells, it looks lichenoid but it’s a deeper infiltrate than lichen planus • Fontana-Masson shows an absence of melanin at the peripheryMalignant Melanoma, Superficial Spreading • Asymmetric proliferation of atypical melanocytes scattered singly and in clusters at all levels of epidermis (buckshot scatter, or pagetoid spread) • Single cells > nests; cells are epithelioid with abundant cytoplasm • Vesicular nuclei with prominent nucleoli, scattered mitotic figures, atypia, tumor growth spreads from one epidermal ridge to another • Epidermis often acanthotic with partial/complete effacement of rete ridges • Associated with mutations in p16, CDKN4a, BRAF, sometimes p53, rasMalignant Melanoma, Desmoplastic Variant • Diffusely infiltrative, sometimes paucicellular, markedly fibrotic dermis • Proliferation of atypical spindle-shaped melanocytes with hyperchromatic nuclei and occasional mitotic figures • Atypical melanocytes as single units and irregular nests in the overlying epidermis • Neurotropism • S100+, but HMB45 negativeMalignant Melanoma, in Situ • Broad poorly circumscribed asymmetrical proliferation of enlarged atypical melanocytes as single units and irregular nests at DE junction • Many atypical melanocytes extending into the upper levels of the epidermis • No atypical melanocytes in the dermisMalignant Melanoma, Lentigo Maligna • Atypical dendritic melanocytes at basal epidermis showing marked cytoplasmic vacuolation and pleomorphic irregular hyperchromatic nuclei • Little tendency to involve upper epidermis • Cells can involve adnexae → goes up and down hair follicles • Pigment often abundant involving full-thickness of epidermis and stratum corneum • Epidermis often atrophic and there is solar elastosis (actinic damage) • Desmoplastic melanomas derive from these, usuallyNevus of Ito/Ota/Mongolian Spot • No junctional activity • In upper and mid dermis are elongated, dendritic, highly pigmented melanocytes scattered among the collagen bundles • Less cellular or even acellular, very few to no melanophagesPigmented Spindle Cell Nevus of Reed • Lesion often shows breadth greater than height • Symmetric, cells are uniform, narrow, elongated, spindle-shaped, often heavily pigmented Dermatopathology  197
  • 46. • Typically junctional or confined to epidermis and papillary dermis, may blend in with adjacent keratinocytes • Arranged in nests (> single cells) and vertically oriented • Nevus cells form compact cluster that pushes the connective tissue aside • Associated with pigmented parakeratosisFigure 5-71. Pigmented Spindle Cell Nevus of ReedRecurrent Nevus • Directly overlying a scar, remnants of a previously excised nevus • Atypical melanocytes at the DEJ in a lentiginous pattern, sharply circumscribed • No mitotic figures • Sharp lateral demarcation, but there can be some upward spreadSpitz Nevus • Symmetric lesion that is wedge-shaped • Presence of junctional cleavage artifact • No involvement of overlying epidermis • Kamino bodies (but not necessary) • Epidermal nests of spindle cells arranged vertically, with lack of cellular cohesion between adjacent cells • No nuclear pleomorphism, a little mitotic activity is okay • Little to no pigmentation classically • Presence of vascular ectasia • Maturation of lesion in deeper levels (decrease in the size of nests and Figure 5-72. Spitz Nevus melanocytes) • Associated with gain of chromose 11p in rare cases5.20 MUSCLEAngioleiomyoma • On low power, a deep tumor that is red and well-circumscribed • High power: Interlacing bundles of uniform smooth muscle cells distributed around numerous small vessels •  Few lesions are so well-circumscribed198  2011/2012 Dermatology In-Review l Committed to Your Future
  • 47. Leiomyoma •  Familial multiple cutaneous leiomyomatosis – gene defect fumarate hydratase • Reddish/orange color → derived from arrector pili muscle • Uniform interlacing bundles or irregular collections of elongated cells with brightly eosinophilic cytoplasm and blunt- ended or cigar-shaped nuclei, mitoses are absent •  Stains positive for desmin and SMALeiomyosarcoma • Ill-defined diffuse lesion, interlacing Figure 5-73. Angioleiomyoma bundles of smooth muscle cells with eosinophilic cytoplasm and blunt-ended, cigar-shaped nuclei • Pleiomorphism in subcutaneous variant more common • Necrotic areas can be seen • Positive for SMA and desmin5.21 NEURALCellular Neurothekeoma (Dermal NerveSheath Myxoma) • Unencapsulated, lobulated mass in dermis with sparing of superficial papillary dermis Figure 5-74. Leiomyoma • Tumor lobules separated by fibrous septa, and composed of stellate and spindle cells with pale indistinct cytoplasm set in an abundant myxoid matrix; occasionally there are bland multinucleated giant cells • Negative for S-100, positive for NKI C3 • Differential diagnosis includes desmoplastic melanoma, dermal Spitz, epithelioid cell histiocytomaGranular Cell Tumor • 40% located on the tongue • Ill-defined, composed of nests of large Figure 5-75. Cellular Neurothekeoma round cells with brightly eosinophilic u TIP granular cytoplasm aAn important clue is pseudoepitheliomatous/epidermal hyperplasia at surface (reminiscent of the epidermis above a dermatofibroma) Dermatopathology  199
  • 48. • Cell borders are indistinct giving a syncytial appearance • Nuclei are uniformly small; commonly, pseudoepitheliomatous hyperplasia of overlying epithelium in tumors of dermis or tongue •  S-100+, Vimentin+, NSE+Neurofibroma • Low power diagnosis • Well-defined, but unencapsulated dermal or subcutaneous; “bubble gum pink” collagenous stroma, nuclei are “tiny dots” • Engorged vessels throughout the Figure 5-76. Granular Cell Tumor tumor; scattered mast cells (a clue) and other inflammatory cells a prominent feature • No collagen trapping as seen in DF • May confuse with DFSP, but DFSP goes through the fat • A plexiform neurofibroma is highly suggestive of neurofibromatosisPalisaded Encapsulated Neuroma (PEN) • Higher in dermis, a well-circumscribed dermal nodule, typically, but may be multinodular or plexiform • Encapsulation is incomplete and superficial part of tumor appears to merge often with surrounding dermis Figure 5-77. Neurofibroma • Cells are arranged in short fascicles separated by artefactual clefting and composed of wavy hyperchromatic nuclei and ill-defined pale eosinophilic cytoplasm • Most cells S-100 positive • Mucosal neuromas in MEN IIb resemble PENsSchwannoma (Neurilemmoma) • Invariably encapsulated, in subcutaneous or deeper tissues; biphasic Antoni A and Antoni B areas • Antoni A → cellular component, closely packed spindle cells with tapering, elongated, wavy nuclei; nuclear Figure 5-78. Palisaded Encapsulated Neuroma palisading produces Verocay bodies; “fence of cells” on either side of a central pink area200  2011/2012 Dermatology In-Review l Committed to Your Future
  • 49. • Antoni B → irregularly scattered spindle or stellate cells in loose myxoid stroma at periphery; within are scattered inflammatory cells and small blood vessels with hyalinized walls • Composed of Schwann cells and are S-100 positiveSupernumerary Digit • Clinically located near the base of the fifth finger • Architecture at low power looks like an acquired digital fibrokeratoma, but there are numerous nerve bundles in the dermis; sometimes there is bone/cartilage as wellTraumatic Neuroma • Unencapsulated mass of numerous axons and Schwann cells embedded in scar tissue adjacent to the cut end of a damaged nerve • Nerve fascicles dispersed haphazardly5.22 PAGETOID SPREADBowen’s Disease • Full-thickness dysplasia including intraepidermal portions of the cutaneous adnexae • Parakeratosis, marked acanthosis, with complete disorganization of the epidermal architecture, loss of maturation, and lack of polarity of cells • Nuclear pleomorphism and mitotic figures seen; clear-cell variant shows marked cytoplasmic vacuolization in upper layers • Sometimes with large keratinocytes that resemble the cells in Paget’s disease of the breast Figure 5-79. Bowen’s Disease • Dyskeratotic cells and acantholysis may be seen (Paget’s disease shows no dyskeratosis and no clear cells) • The basal layer is more uniform and looks like eyeliner (i.e., “eyeliner sign”) • Stain for high-molecular weight keratins (cytokeratin+)Metastatic Breast Carcinoma with Epidermotropism • Epidermis can look like Paget’s disease • Key is in the dermis, where there are neoplastic cells infiltrating single-file through collagen, with some aggregation into duct-like structures • Lots of atypia (unlike microcystic adnexal carcinoma, which shows no atypia) • No grenz zone like AMML •  CEA+, CK7+Pagetoid Melanoma • The basal layer should have atypical melanocytes • CEA-negative, S100+ Dermatopathology  201
  • 50. Paget’s Disease of the Breast/Extramammary Paget’s • All variants show identical histology • Epidermis often acanthotic, with varying amounts of parakeratosis or hyperkeratosis • Infiltration with large cells with abundant pale-staining cytoplasm containing large vesicular nuclei; the unique feature is the gray/blue cytoplasm • Cells can be scattered throughout all layers of epidermis • Unlike melanoma, there are areas where proliferation is strictly above the basal layer • Frequently positive with Alcian blue pH 2.5, colloidal iron, or mucicarmine stains; stains positive for PAS, CEA, EMA, CAM5.2, u TIP and low molecular weight keratin aA clue to Paget’s disease of the breast is recognizing nipple (smooth muscle bundles in the dermis, sometimes ducts)Much Rarer • Pagetoid reticulosis (Woringer-Kolopp: localized disease in younger patients on acral areas; Ketron-Goodman: widespread disease) • Intraepidermal spread of sebaceous carcinoma or Merkel cell carcinoma5.23 PALISADING REACTIONSGout • Histiocytes, some palisaded, surrounding a basophilic aggregate, which on higher power has some crystalline features (silvery needle-like clefts) • Formalin fixation can destroy urate crytals (need alcohol fixation)Granuloma Annulare (GA) • Palisading granuloma, sometimes interstitial, with histiocytes surrounding a focus of altered collagen that often has a bluish tinge secondary to mucin; the palisading granulomas are in discrete foci in the dermis Figure 5-80. Gout • Note that giant cells and plasma cells are more commonly seen in necrobiosis lipoidica diabeticorum • Note that deep GA can look exactly like a rheumatoid nodule, and the slide may lack epidermisNecrobiosis Lipoidica Diabeticorum (NLD) • Square biopsy, thin epidermis with no rete ridges Figure 5-81. Granuloma Annulare202  2011/2012 Dermatology In-Review l Committed to Your Future
  • 51. • “Layered” superficial and deep dermal infiltrates (multifocal), separated by areas of degenerated collagen (necrobiosis, dripping of red areas through the dermis), infiltrate consists of lymphocytes, histiocytes, and plasma cells • Elastic-van-Gieson stain shows complete absence of elastic tissue • Plasma cells and giant cells are more numerous than in GANecrobiotic Xanthogranuloma • Granulomatous inflammation surrounding central necrobiosis and cholesterol clefts, may see lymphoid follicles • Large areas of marked necrobiosis alternate with foci of xanthogranulomatous infiltrate in reticular dermis into subcutaneous fat • Necrobiotic collagen appears as amorphous eosinophilic debris • Infiltrate composed of lymphocytes, epithelioid cells, foamy histiocytes, and conspicuous giant cells, many of which are Touton type, and others are bizarre and angulated • Compared with NLD and subcutaneous GA, the necrobiosis of NXG is far more extensive, occurring in broad bands with extensive infiltrates of Touton giant cells and foamy histiocytes • Associated with paraproteinemiaRheumatoid Nodule • Epidermis is often not represented on the slide (a deep lesion) • Dense deposit of fibrin (confluent, large, eosinophilic) with surrounding palisading (“picket fence”) of histiocytes – palisade is tight, typically located in subcutaneous fat or in deep reticular dermis • Consider deep GA, especially if the specimen is from a child5.24 VASCULAR Figure 5-82. Rheumatoid NoduleAcroangiodermatitis of Mali • Can look like Kaposi’s clinically • Biopsy shows exaggerated stasis changes with thick “reduplicated” vessels, extravasated RBCs, hemosiderin, fibrosis u TIPAngiokeratoma a5 types: Mibelli • Numerous dilated and congested capillaries in the papillary dermis Corporis diffusum with overlying acanthosis and hyperkeratosis of the epidermis Circumscripta • Thrombosis is common Papular • In Fabry’s disease there are cytoplasmic vacuoles representing Fordyce lipidsAngiolymphoid Hyperplasia • Often on the face • Intradermal ill-defined, lobulated mass of numerous vascular channels lined by large rounded endothelial cells with copious eosinophilic cytoplasm → the endothelial cells are protuberant and extend into the vessel lumen Dermatopathology  203
  • 52. • Each vessel is separate; sometimes prominent inflammatory cell infiltrate of lymphocytes, eosinophils and histiocytesAngiosarcoma • Often on scalp/sun exposed areas of elderly • Ill-defined infiltrative intradermal mass of numerous anastomosing, clefting vascular channels of varying caliber that dissect (carve) through the collagen • Endothelium that is single- or double- layered and plump, pleomorphic and mitotically active (highly atypical) → Figure 5-83. Angiolymphoid Hyperplasia forming papillae or solid nests within vascular lumina • Stains with CD31 • Under EM there are Weibel-Palade bodies • Stewart-Treves: angiosarcoma devel- oping in lymphedematous area (originally described in post-mastectomy lymphedema)Bacillary Angiomatosis • Lobules of capillaries with prominent vascular endothelial cells with “blue clouds” of organisms located adjacent to vessels • Neutrophilic infiltrate with leukocytoclasis Figure 5-84. Angiosarcoma • Look for ulceration • Need to stain organisms with Warthin- StarryGlomus Tumor • Common acrally (subungual), can be paroxysmally painful • Derived from contractile cells of the Sucquet-Hoyer canal and are desmin- positive • Very uniform round cells around vascular spaces (the spaces can be quite dilated and resemble a cystic structure) • Solid tumors are composed of sheets of uniform cells that might only be two Figure 5-85. Glomus Tumor cells thick; don’t confuse with eccrine spiradenoma • Stains positive for smooth muscle actin, muscle-specific actin, and myosin • An inherited form is autosomal dominant with numerous tumors that are non-painful and located on the trunk/extremities; histologically are often glomangiomas204  2011/2012 Dermatology In-Review l Committed to Your Future
  • 53. Intravascular Papillary Endothelial Hyperplasia (Masson’s) • Thrombosed vessel (circular space with pink fibrin within) with papillated fronds projecting into the center; the fronds are lined by a single layer of endothelial cells • No atypiaKaposi’s Sarcoma • Early patch: Increase in dermal vessels showing minimal atypia and admixture of lymphocytes and plasma cells associated with hemosiderin deposits and purpura; vessels oriented parallel to epidermis and may dissect between collagen bundles; trapping of RBC’s; a clue is the promontory sign where there are new vessels (clefts) forming around other vessels/adnexae • Plaque stage: Obvious and extensive dermal vascular proliferation with lumina varying considerably in caliber; Figure 5-86. Kaposi’s Sarcoma prominent inflammation • Nodular stage: Well-circumscribed dermal mass of variably eosinophilic spindle cells, scattered between cells are numerous irregular, slit-like, vascular spaces lacking endothelial lining • Spindle cells are CD34-positive and focally positive for CD31; Ulex – positive; Factor VIII positive • HHV-8 positiveLiposarcoma, Myxoid • Complex plexiform network of small thin- walled capillaries in a pattern resembling chicken-wire • Myxoid stroma Figure 5-87. Kaposi’s Sarcoma • Deep lesionLymphangioma, Cavernous • Widely-dilated, irregularly shaped spaces in dermis and subcutaneous tissue lined by single layer of bland endothelial cells • Milky white substance in vesselsPyogenic Granuloma • Exophytic, lobulated, dermal mass of numerous small capillaries • Very cellular; often radiating from larger, more central vessels, in a loose edematous collagenous matrix • Mitoses commonly present, adjacent epidermis often acanthotic and forms collarette • No trapping of RBC’s Dermatopathology  205
  • 54. Sclerosing Hemangioma • Like a fibrous histiocytoma with hemosiderin thrown in • The periphery of the tumor resembles a DF with collagen trapping; there can be foamy cells and multinucleated giant cells • Look for RBC’s trapped between spindle cells5.25 MISCELLANEOUSAcanthosis Nigricans • Elongated papillomatosis • Hyperkeratosis • Slight acanthosis Figure 5-88. Pyogenic Granuloma • Occasional keratin-filled cystsAccessory Tragus • Polypoid papule • Periphery rimmed by vellus hairs (near epidermis) • Cartilage might not be present; if cartilage present it is at center of polyp and surrounded by abundant adipose tissueAmalgam Tattoo • Mucosal surface • Dermal pigment which is deposited in a very fine, wiggly pattern • Occasional clumping Figure 5-89. Accessory TragusChloroma • Greenish tumor (grossly) in acute granulocytic leukemia • Green color secondary to myeloperoxidase • Diffuse infiltrate in dermis with many blast cells • Chloracetate esterase-positiveChondrodermatitis Nodularis Helicis • Not always an ulcer; the key is fibrosis or degenerated collagen beneath an ulcer or hyperplastic epidermis • Granulation tissue flanks the fibrosis • Base contains abundant granulation Figure 5-90. Chondrodermatitis Nodularis Helicis tissue and heavy chronic inflammatory cell infiltrate, often degenerative changes in cartilage with hyalinization or calcification206  2011/2012 Dermatology In-Review l Committed to Your Future
  • 55. Clear Cell Acanthoma • Clue is that it looks like psoriasis, with regular acanthosis, but the cells are clear/pale, and at low power you can see an abrupt change on each lateral margin from clear/pale cells to normal-appearing, less acanthotic epidermis •  Associated with ichthyosis •  Clear/pale cells secondary to increased glycogen content secondary to a deficiency of phosphorylase • PAS-positiveComa Blister • Akin to erythema multiforme of the sweat glands → eccrine glands are red and necrotic • Both intra- and subepidermal blister can form • Caused by hypoxemiaElastosis Perforans Serpiginosa (EPS) • Perforating disorder with elimination of basophilic elastic fibers through the epidermis • Increased elastic tissue in dermis and papillae filled with homogeneous coarse elastic fibers • Center of papule has a plug that fills a winding or straight canal unrelated to pilosebaceous unit, extending from papillary dermis to skin surface • Surrounding epidermis hyperplastic and acanthotic and sometimes Figure 5-91. Electrodessication Artefact pseudoepitheliomatous, growing downward to engulf abnormal elastic fibers in a claw-like fashion PEARL w  Associated with Down’s syndrome, Ehlers- Danlos type IV, Osteogenesis imperfecta, Rothmund Thompson, Marfan’s, Werner’s, acrogeria, penicillamineElectrodessication Artefact • Epithelial cells become elongated and spindled like “chafs of wheat” • Streaming of nuclei • Collagen amorphous and blueEndometriosis, Cutaneous Figure 5-92. Endometriosis, Cutaneous • Dilated ducts, endometrial glands lined by tall columnar epithelium • Fibrovascular core (stroma) around ducts that appear apocrine • Often deeper in dermis with associated hemorrhage Dermatopathology  207
  • 56. Eosinophilic (Pustular) Folliculitis • Histologically the three forms look similar: eosinophil-rich pustule, spongiosis of outer root sheath of hair follicle, superficial and deep perifollicular and perivascular lymphocytic infiltrate with eosinophils, neutrophils PEARLw  linically there are probably three different C forms, one seen as crusted papules on the occipital scalp of babies, another seen more in Japanese patients on the face, and another consisting of pruritic papules on the trunk of HIV patients Figure 5-93. Eosinophilic (Pustular) FolliculitisErythema Dyschromicum Perstans • Hyperkeratosis with normal or atrophic epidermis; basal cell vacuolar degeneration and cytoid body formation • Marked pigmentary incontinence • Mild perivascular or lichenoid inflammatory cell infiltrate in superficial dermisFreeze Artefact • Empty vacuoles throughout epidermisGel Foam Artefact • Wavy foreign substance Figure 5-94. Erythema Dyschromicum PerstansOchronosis • Exogenous and endogenous histopathology identical • Banana-shaped brownish to orange- yellow thickened, discolored collagenMerkel Cell Carcinoma • Very blue on low power but cells are very pale on high power • Shows nodules and sheets of basophilic cells with vesicular nuclei containing small nucleoli and inconspicuous cytoplasm • Tumor cells can dissect through collagen, marked mitotic activity; tumors Figure 5-95. Gel Foam Artefact stain positive for neuron specific enolase, EMA, Ber-EP4, CAM5.2, CD57208  2011/2012 Dermatology In-Review l Committed to Your Future
  • 57.  • Characteristic paranuclear globular coexpression of simple epithelial cytokeratins (CK20) and neurofilament proteins • Metastatic oat cell carcinoma looks the same but stains negative for cytokeratin 20 and is positive with TTF-1 • Associated with Merkel cell polyomavirusNecrolytic Migratory Erythema • Necrosis of the superficial epidermis (relative sparing of the lower epidermis) (the necrosis can look like confluent Figure 5-96. Ochronosis parakeratosis) • Intraepidermal clefting and vesiculation • Differential includes other nutritional deficiencies like zinc deficiency (acrodermatitis enteropathica), pellagra, biotin deficiencyParaffinoma • Round or oval spaces within the dermis and subcutaneous fat in a “swiss cheese” pattern • Foamy histiocytes or giant cells may line edges of these cystic spaces, and dense fibrous scarring may be evident Figure 5-97. Merkel Cell CarcinomaReactive Perforating Collagenosis • Widened dermal papilla contains basophilic debris without inflammation – “volcano effect” • Overlying epidermis thinned, and perilesional epidermis acanthotic and envelops altered collagen • Looks like an ulcer, and fibers carried to surface by widened intercellular spaces • In umbilicated lesions epidermis forms a cup-shaped depression with parakeratotic keratinocytic debris and degenerated vertically oriented collagenRenal Carcinoma, Metastatic • Blood vessels are the clue to the diagnosis → very vascular; bubbly, clear cells with some mitoses and cytologic atypiaStoriform Collagenoma (Sclerotic Fibroma) • Well-circumscribed dermal nodule composed of hyalinized collagen bundles separated by clefts and arranged in a storiform pattern • Hypocellular • Cowden’s syndrome or Gardner’s syndrome Dermatopathology  209
  • 58. Urticaria Pigmentosa • Mast cells seen predominantly in papillary dermis • Eosinophils present often, basal cell hyperpigmentation of overlying epidermis commonly, blistering can occur subepidermally • Can stain with Giemsa, Leder, or toluidine blue; as well as tryptase and c-kit • Monomorphic cell differential diagnosis, which includes mastocytosis, glomus tumor, and poromaXanthelasma • Important clue is recognizing eyelid skin, either by vellus hair follicles or skeletal muscle at the base of the biopsy • Lipid laden foam cells within superficial dermisXanthoma, Eruptive • Foamy histiocytes within superficial reticular dermis • Lymphocytes and neutrophils may infiltrate • Always check for foam cells if you are thinking GA5.26 CLUES FOR BOARD PURPOSESIf the epidermis is absent, think of: • Angioleiomyoma • Giant cell tumor of tendon sheath • Nodular fasciitis • Rheumatoid nodule • Gout • HibernomaIf the section looks normal at low power, think of: • Macular amyloidosis • Anetoderma • Argyria • Atrophoderma • Café-au-lait spot • Connective tissue nevus • Cutis laxa • Dermatophyte infection • Tinea versicolor • GVHD • Ichthyosis vulgaris • Myxedema • Parapsoriasis • Porokeratosis • Scleroderma • Scleromyxedema • Urticaria • TMEP • Vitiligo210  2011/2012 Dermatology In-Review l Committed to Your Future
  • 59. If there is necrosis in the epidermis, think of: • Nutritional deficiency (if confluent superficial necrosis below stratum corneum, with sparing of lower epidermis) • Erythema multiforme (if full-thickness necrosis with a normal basket-weave stratum corneum) • Herpes (if necrosis in small foci or associated with a follicle and intermixed with balloon cells/giant cells/cells with basophilic viral changes) • Coma bullae (look for necrosis of eccrine glands)If you see giant cells, think of: • Reticulohistiocytosis (if pale pink and “oncocytic”) • Juvenile xanthogranuloma (if Touton) • Xanthoma (if many Touton with foamy cells) • Tuberculosis (if Langhans and foreign-body) • Herpes (if associated with necrosis and balloon cells) • Scar (if foreign-body) • Ruptured cyst (if foreign-body) • Giant cell tumor of tendon sheath (if osteoclast-like)If you see regular acanthosis at low power, think of: • Psoriasis • Bowen’s (look for atypia/mitoses) • Clear cell acanthoma (look for pale cells with abrupt demarcation to normal) • Dermatophytosis (hyphae within stratum corneum)If you see neutrophils in the stratum corneum, think of: • Psoriasis • Dermatophytosis • Pityriasis lichenoides • Verruciform xanthomaIf you see parakeratosis above basket-weave stratum corneum, think of: • Dermatophytosis • Resolving spongiotic disorderIf you see pseudoepitheliomatous hyperplasia overlying abscesses, think of: • Blastomycosis (look for broad-based budding organisms 8-15 microns) • Paracoccidioidomycosis (look for 60 micron mariner’s wheel; single yeast cells will be 6-20 microns) • Chromoblastomycosis (look for pigmented 6-12 micron “copper pennies”) • Coccidioidomycosis (look for 10-80 micron spherules) • Sporotrichosis (cigar-shaped organisms that are very rare on biopsy) • Halogenoderma/Bromoderma (note that this diagnosis is history-dependent and needs exclusion of infections, so it is unlikely that you will make this diagnosis on the Boards)If you see grains, think of: • Botryomycosis (look for “blue clouds” of bacteria surrounded by eosinophilic material in the Splendore-Hoeppli reaction) Dermatopathology  211
  • 60. • Actinomycosis/Nocardiosis (look for thin filaments at periphery of grain) • Eumycetoma (look for thick hyphae at periphery of grain) Gram-positive sulfur granules differential: • Staphylococcal abscess • Actinomycosis (pink and filamentous at the edge of lesion) • Nocardia (can visualize organisms with Fite stain)If you see hyperkeratosis over an atrophic epidermis, think of: • Lichen sclerosus et atrophicus • Flegel’s disease • Discoid lupus erythematosusIf you see a dome-shaped/cone-shaped silhouette at low power, think of: • Accessory digit (look for nerves in dermis) • Acquired digital fibrokeratoma (hyperkeratosis, dermal fibrosis) • Accessory nipple (hyperpigmented acanthosis, smooth muscle bundles in dermis, ducts in deep dermis) • Accessory tragus (numerous vellus/small hair follicles in dermis/cartilage may be present)If you see a very rectangular-shaped punch biopsy “i.e., square biopsy sign,” think of: • Scleromyxedema • Scleredema • Scleroderma • Necrobiosis lipoidica diabeticorumIf you see clear cells, think of: • Metastatic renal cell carcinoma (look for hemorrhage) • Clear cell squamous cell carcinoma/Bowen’s (look for atypia/mitoses/squamous pearls) • Trichilemmoma (look for palisading of basal layer and thick basement membrane) • Clear cell acanthoma • Hidradenoma • Note: make sure the cells are clear cells, not balloon cells or sebaceous cellsIf you see eosinophilic spongiosis, think of: • Incontinentia pigmenti, pemphigus, BP, chronic bullous disease of childhood, pemphigoid gestationis, PUPPP, insect-bite reactions, atopic dermatitis, contact dermatitis, Grover’s disease, drug reaction • There is clearing of keratinocytes with indwelling eosinophils, but no abscess formation5.27 “BODIES”Asteroid Body • Eosinophilic amorphous material seen in sporotrichosis OR • Stellate inclusions seen in sarcoid, berylliosisBirbeck Granules • Seen on electron microscopy • Tennis-racquet-shaped cytoplasmic bodies in Langerhans cells212  2011/2012 Dermatology In-Review l Committed to Your Future
  • 61. Caterpillar Body • Pale amorphous pink linear structures in the epidermis of porphyria cutaneous tarda • Represents type IV collagenCivatte Body • Apoptotic cell remnants in epidermisColloid Body • Apoptotic cell remnants in papillary dermisComma-shaped Body • Seen on electron microscopy • Associated with histiocytoses like benign cephalic histiocytosis (non-specific)Cowdry A body (Lipschutz Body) • Intranuclear eosinophilic globules seen in herpes infectionCowdry B Body • Intranuclear inclusions seen in adenovirus and poliovirus infectionDonovan Body • Intracytoplasmic bacteria in granuloma inguinaleDutcher Body • “Pseudo”-nuclear inclusions secondary to collections of immunoglobulin in the cytoplasm that push into the nucleus of plasma cellsGuarnieri Body • Eosinophilic cytoplasmic inclusions seen in smallpoxHenderson-Paterson Body • Large eosinophilic cytoplasmic inclusions that fill the cell seen in Molluscum lesionsKamino Body • Eosinophilic globular masses of varying sizes seen at and above DEJ • Considered to be a helpful marker for Spitz nevusLeishman-Donovan Body • Intracytoplasmic, nonflagellated parasite seen in leishmaniasisLipschutz Body (Cowdry A Body) • Intranuclear inclusions in epithelial or neuronal cells seen in herpes infectionMedlar Body • a.k.a. sclerotic body, “copper penny,” hot cross bun • Seen in chromoblastomycosisMichaelis-Gutman Body • Concentric, laminated, calcified bodies within and external to cells seen in malakoplakia Dermatopathology  213
  • 62. Negri Body • Cytoplasmic inclusions (neuronal) seen in rabiesPapillary Mesenchymal Body • Structure thought to be an abortive attempt of fibroblasts to form mesenchyme necessary for hair induction, reminiscent of early hair germ • Seen in trichoblastoma and trichoepitheliomaPsammoma Body • Concentric, laminated, calcified bodies seen in papillary thyroid carcinoma, benign nevi, meningiomas, and other conditionsRussell Body • Inclusions secondary to collections of immunoglobulin in the cytoplasm of plasma cells • Seen in rhinoscleroma, granuloma inguinale, syphilisSchaumann Body • Concentric, laminated, calcified inclusions seen in sarcoid and other granulomatous disordersVerocay Body • Palisaded nuclei on either side of a central pink area in schwannomaWeibel-palade Body • Cytoplasmic marker of endothelial cellsWorm-shaped Body • Seen on electron microscopy • Associated with histiocytoses like benign cephalic histiocytosis (non-specific)Zebra Body • Seen on electron microscopy in mucopolysaccharidosesACKNOWLEDGMENTSRonald Barr, MDScott Binder, MDBruce E. Strober, MD, PhDREFE RE N C E S1. Alam M, Caldwell JB, Eliezri YD. Human papillomavirus-associated digital squamous cell carcinoma: Literature review and report of 21 new cases. J Am Acad Dermatol 2003; 48: 385-393.2. Allee JE et al. Multiply recurrent trichilemmal carcinoma with perineural invasion and cytokeratin 17 positivity. Dermatol Surg. 2003; 29: 886-889.3. Binder SW et al. The histology and differential diagnosis of Spitz nevus. Sem Diag Pathol 1993; 10: 36-46.4. Elder D et al, eds. Lever’s Histopathology of the Skin, 8th ed. Philadelphia: Lippincott, 1997.5. Fetil E et al. Multiple pilomatricoma with perforation. Int J Dermatol. 2002; 41: 892-893.214  2011/2012 Dermatology In-Review l Committed to Your Future
  • 63. 6. Glusac EJ. Criterion by Criterion, MF. Am J Dermatopathol 2003; 25: 264-269.7. Hoque SR et al. Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathological, immunophe- notypic and molecular analysis of six patients. Br J Dermatol 2003; 148: 516-525.8. Poniecka AW et al. An immunohistochemical study of basal cell carcinoma and trichoepithelioma. Am J Dermatopathol 1999; 21: 332-336.9. Rutten A et al. Cystic sebaceous tumors as marker lesions for the Muir-Torre syndrome: a histopath- ologic and molecular genetic study. Am J Dermatopathol 1999; 21: 405-413.10. Said J et al. Lymphoma including Hodgkin lymphoma. In Immuno and Molecular Microsocopy, in press.11. Sardy M et al. Epidermal transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis. J Exp Med 2002; 195: 747-757.12. Terrier-Lacombe MJ et al. Dermatofibrosarcoma protuberans, giant cell fibroblastoma, and hybrid lesions in children: clinicopathologic comparative analysis of 28 cases with molecular data—a study from the French Federation of Cancer Centers Sarcoma Group. Am J Surg Pathol 2003; 27: 27-39.13. Weedon D. Skin Pathology, 2nd ed. CITY: Churchill Livingston, 2002.14. Wu H, Stanley JR, Cotsarelis G. Desmoglein isotype expression in the hair follicle and its cysts cor- relates with type of keratinization and degree of differentiation. J Invest Dermatol 2003; 120: 1052- 1057.15. Feng H. Shuda M, Chang Y. Moore PS. Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma. Science 2008; 319: 1096-1100. Dermatopathology  215
  • 64. NOTES216  2011/2012 Dermatology In-Review l Committed to Your Future
  • 65. NOTES Dermatopathology  217
  • 66. NOTES218  2011/2012 Dermatology In-Review l Committed to Your Future