Elston Chapter 1 Basics Flashcards
Anaplasia
atypical nuclei and pleomorphism
Asteroid body
collections of eosinophilic material seen in sporotrichosis also refers to star-shaped intracytoplasmic inclusions seen in giant cells of sarcoidosis or berylliosis or other granulomatous process
ballooning degeneration
destruction of epidermis by dissolution of cell attachments and intracellular edema
caterpillar bodies
pale pink linear basement membrane material within epidermis seen in PCT, represents degenerated type IV collagen
civatte/colloid bodies
pink, globular remnants of keratinocytes (lichen planus)
cornoid lamellae
45 degree anle parakeratosis in a column above a focus with diminished granular layer and underlying dyskeratotic cells
corps ronds/grains/dyskeratosis
corps ronds =- rounded nucleus with ahlo of poale to pink dyskeratotic cytoplasm corps grains = dark blue flattened nucleus surrounded by minimal cytoplasm dyskeratosis = abnormal individual-cell keratinization
Cowdry A body
also known as Lipshutz body intranuclear pink inclusions of herpesvirus infections
Cowdry B body
intranuclear pink inclusions of adenovirus and poliovirus infection
Donovan body
intracytoplasmic collectinos of bacteria seen in granuloma inguinale
Dutcher body
intracytoplasmic pink masses of immunoglobulin that invaginate into the nucleus of plasma cells and appear to be intranuclear
epidermolytic hyperkeratosis
coarse, irregular hypergranulosis associated with disruption of cell membranes associated with keratin 1 and 10 mutations
festooning
papillary dermis retains undulating pattern (often in PCT)
flame figure
collagen encrusted with major basic protein from eosinophils
guarnieri body
eosinophilic inclusions of smallpox
henderson-paterson body
intracytoplasmic oval, pink inclusions of molluscum infection
hyper/hypopigmentation
increased/decreased melanin pigment
kamino body
dull pink to amphophilic basement membrane material within epidermis in Spitz
koilocytes
keratinocytes with clear cytoplasm and shrunken raisin-like pyknotic nuclei
medlar body
chromomycosis copper penny spores brown round structure resembling overlapping copper pennies divide by septation, resembling a hot-cross bun
michaelis-gutman body
intra-and-extracellular calcified, concentric circular structures, seen in malakoplakia
papillary mesenchymal body
structure resembling whorl of plump mesenchymal cells normally present in the hair papilla (seen in trichoblastoma and trichoepithelioma)
Psammoma body
extracellular laminated, calcified structures seen in meningioma, papillary thyroid carcinoma, ovarian carcinoma
pseudoepitheliomatous hyperplasia
acanthosis of adnexal epithelium and epidermis mimcking SCC, often a/w trapping of elastic fibers
pseudohorn cyst
keratin-filled cystic structure result of cutting through invaginations of stratum corneum (connects to surface)
reticular degeneration
destruction of epidermis with cell membranes remaining in a net-like pattern
russell body
intracytoplasmic pink inclusions of fIg in plasma cells, seen in rhinoscleroma and other conditions with many plasma cells
Schaumann body
laminated calcified structure seen in sarcoidosis
verocay body
composed of 2 nuclear palisades enclosing pink cytoplasmic processes, seen in schwannoma
eyelid and ear skin
have many vellus hair follicles; eyelid skin has skeletal muscle in upper dermis
conjunctival side of eyelid skin has no stratum corneum or hair follicles, does have goblet cells
Areolar skin
slight acanthosis with basilar hyperpigmentation
sometimes central invagination of epidermis that leads to follicle and sebaceous glands
smooth muscle bundles in mid-deep dermis
apocrine glands in the reticular dermis
acral skin
compact eosinophilic stratum corneum
slight papillomatosis on dorsal surfaces
volar skin
compact eosinophilic hyperkeratosis with underlying stratum lucidum
no hair follicles or sebaceous glands
eccrine glands numerous
Meissner and Pacinian corpuscles can be seen
Mucosa
absent granular layer
keratinocytes large and pale (filled with glycogen)
dilated vessels in submucosa
can get smooth muscle bundles
nasal turbinate
erectile tissue with fibrous septa and vascular sinusoids and mucous glands
fetal skin
stellate and spindled fibroblasts (mesenchyme)
densely cellular
Hair anatomy
infundibulum - from epidermis to insertion of sebaceous gland
isthmus - from insertion of sebaceous gland to insertion of arrector pili muscle (bulge)
stem - from insertion of arrectorp ili muscle (bulge) to Adamson’s fringe (only present in anagen hairs)
Bulb - below the step of anagen hair follicle, from Adamson’s fringe to base of hair follicle
hair infundibulum
from epidermis to insertion of sebaceous gland
intraepidermal portion = acrotrichium
keratinizes in pattern of normal epidermis with granular layer
hair isthmus
from insertion of sebaceous gland to insertion of arrector pili muscle (bulge)
keratin formed in ABSENCE of granular layer = trichilemmal keratinization
inner root sheath is lost at this level and outer rooth sheath develops an inner corrugated, dense pink cornified layer; peripheral palisading of the outer root sheath is seen
Adamson’s fringe (Hair)
point above which hair cornifies
dermaotophytes only infect cornified hair above Adamson’s fringe
above Adamson’s fringe, Huxley’s layer of the inner root sheath no longer has trichohyalin granules
hair tends to retract from the inner root sheath above Adamson’s fringe
the inner root sheath is fused and blue-gray at this level and trichohyalin granules are not seen
the outer root sheath is composed of pink cells with peripheral palisading
Bulb
below stem portion/from Adamson’s fringe to base of hair follicle
3 zones: matrix, supramatrix, keratogenous zone
matrix - from base to critical line (widest point of bulb and papillae)
supramatrix - from critical line to B-fringe (point at which outer root sheath becomes multilayered and Henle’s layer no longer has trichohyaline granules)
keratogenous zone - from B-fringe to Adamson’s fringe
layers of the hair follicle that can be seen: fibrous root sheath, vitreous basement membrane zone, outer rooth sheath, inner root sheath (henle’s layer, huxley’s layer, cuticle of inner root sheath), hair shaft (cuticle of hair shaft, cortex), medulla
anagen vs telogen hairs
anagen hairs have stem and bulb producing hair shaft
telogen hairs lack inferior segment
telogen hairs are easily recognized in vertical sections as the club hair and surrounding trichilemmal keratin give the imrpession of a flame thrower
eponychium
visible cuticle - thick keratinous material boarders proximal nail fold and adheres to nail plate
true cuticle is located beneath the visible portion and is derived from teh ventral proximal nail fold
hyponychium
everything ventral to nail plate
solehorn
subungual white to colorless keratin extending from ditsal nail bed underheath the onychodermal band to below the free,distal edge of the nail plate
types of keratinization of the nail
onychokeratinization (no granular layer) ard keratin of nail plate
onycholemmal keratinization - ventral part of proximal nail fold (has granular layer), bed epithelium (cuticle, bed horny layer, solehorn) no granular layer
epidermoid keratinization - dorsal proximal nail fold, lateral folds, hyponychium
dermal dendrocytes
macrophage-type cell in dermis; many are factor 13a positive, some are S100 positive
likely serve as antigen presenting cells
giant cell types
foreign body - ncueli haphazard
Langerhans - nuclei in wreath shape
Osteoclast-like - ncueli haphazard and eccentric; cytoplasm deep pink with scallooped border that molds to adjacent cells
touton - ncuel in wreath with foamy cytoplasm peripherally
ringed siderophage - touton with hemosiderin (characteristic of fibrous histiocytoma type of DF)
histiocytes
epithelioid cell with central round/oval nucleus and surrounding cytoplasm
tend to coalsecein tissue without intervening connective tissue
phagocytosis and antigen presentation
Langerhans cell
dendritic cells in epidermis and dermis
CD1a+, S100+ peanut agglutinin, langerin +
reniform with eccentric nucleus
originate in bone marrow
contain birbeck granuels, tennis-racked-shaped rod and oval bodies seen in EM
Th1 vs Th2 cytokines
Th1 cells prdouce IL-1, IL-2, IL-12 and IFN-gamma and are important for cell-mediated immunity and function in activating macrophages
TH2 cells produce IL-4, IL-5 and IL-10 and are important for humoral immunity
what cytokine induces eosionphil production
IL-5
eosinophils contain
major basic protein, eosinophil cationic protein, catalase and other proteins
Masson’s trichrome
collagen - blue green
smooth msucel - red
ex) scar (blue-green) vs leiomyoma (red)
pitfall: young collagen can stain red
Verhoeff-Van Gieson
stain elastic fibers black
ex) absence or reduction in scar, mid-dermal elastolysis, anetoderma, cutis laxa
ex) distorted fibers in PXE
get beaded elastic fibers in elastofibroma dorsei
toluidine blue
stains mast cell granules metachromatically
also stains mucin/acid mucopolysaccharides
can use in urticaria pigmentosa to get metachromatic staining
Leder stain
naphthol ASD choracetate esterase
mast cell cytoplasm stains red (not dependent on presence of granules)
also stains myeloid cells (eg leukemia cutis)
name 2 mast cell stains
toluidine blue
leder
Name 5 carbohydrate stains
PAS, alcian blue, colloidal iron, toluidine blue, mucicarmine
mucicarmine stains
acid mucopolysaccharides pink to red - stains mucinous capsule of Cryptococcus neoformans pink to red
colloidal iron stains
acid mucopolysaccharides blue
hyaluronidase digestion can be combined with colloidal iron to differentiate between hyaluronic acid and other mucosubstances
Alcian blue stains
acid mucopolysaccharides blue
in normal skin, most mucin is sulfated acid mucopolysaccharide (heparin, chondroitin, and dermatan sulfates)
in most patholgoic states with increased dermal mucin, mucin is prdominantely non-sulfated hyaluronic acid
non-sulfated acid mucopolysaccharides (hyaluoronic acid) stain with Alcian blue at pH 2.5 but not pH0.5
ex) follicular mucinosis, GA, myxoid cyst, dermal mucin in lupus
Sulfated acid mucopolysaccharides stain with Alcian blue at both pH 2.5 and pH 0.5
can use with or without hyaluronidase to differentiate hyalulronic acid from other mucopolysaccharides
PAS stains what
glycogen, neutral mucopolysaccharides (like BM), and fungi
glycogen is diastase labile, ie. sections exposed to diastase before staining do not stain red with PAS
useful for clear cell acanthoma and trichilemomma
fungai and neutral mucopolysaccharides (basement membrane) are diastase resistant
can see thickened vessel walls in porphyria
acid mucopolysaccharides (hyaluronic acid) do not stain with PAS
amyloid stains with what 3 stains
congo red - stains brick red and has apple green birefringence withp olarized light
thioflavin T - yellow to yellow-green with fluorescent microscope
Crystal violet - metachromatic stain for red-purple amyloid color
Iron stains with what?
Prussian blue (Perls stain) - ferric ions react to form a deep blue color
distinguish melanin from hemosiderin
does not ID iron in intact RBCs
Melanin stains with what
Fontana-Masson - silver stain resulting in black precipitate with melanin
calcium stains with what 2 stains?
von kossa - silver stain stains calcium salts black (PXE, calcinosis cutis, calciphylaxis)
Alizarin red - binds directly to calcium ions resulting in orange-red color
lipids stain with what stains?
oil red O
sudan black
osmium tetroxide
all require fresh tissue
bacteria stain with
Brown Hopps - modification of Brown-Brenn technique; gram positive stains blue and gram negative stains red
Fungi stain with what 2 stains
PAS - PAS positive and diastase resistant
GMS (Grocott’s methenamine silver) - gray-black reaction with fungal walls, also stains Nocardia and Actinomyces
Mycobacteria stain with what 4 stains?
Ziehl-Neelsen acid-fast tain
Fite acid fast stain
Kinyoun’s acid fast stain
mycobacteria stain bright red
fite is preferred for partially acid-fast organisms such as lepra bacilli, atypical mycobacteria and Nocardia - it preserves color due to use of peanut oil and gentle decolorization
Auramine-rhodamine - mycobacteria fluoresce reddish yellow with fluorescent microscope
Spirochetes stain with what stains?
Warthin-Starry, Dieterle, Steiner (modeified Dieterle)
silver stains stain black spirochetes
ex) lyme (around vessels and in dermal papillae), syphilis (lower epidermis)
also stains Legionella, Bartonella and Donovan bodies of granuloma inguinale
Giemsa stains what organisms and features?
myeloid and mast cell granules purplish blue
bacteria, Leishmania and Histoplasma
AE1/AE3 stains what?
cocktail of higha nd low molecuar weight monoclonal cytokeratin antibodies
stains epdermis and adnexal epithelium
stains all epithelial tumors (SCC and adnexal)
also stains epithelioid sarcoma, synovial sarcoma and mesothelioma
pankeratin/CK polyclonal keratin is used rather than AE1/AE3 why?
greater sensitivity
p63 is expressed where
basal and spinous cells of epidermis
germinative cells of sebaceous glands
myoepthelial cells of sweat glands
NOT reactive in metastatic carcinoma –>helps differentiate from primary cutaneous adnexal neoplasms
reactive in cutaneous spindle cell SCC
CAM5.2 detects low molecular weight cytokeratines present in what?
glandular neoplasms
does not stain epidermis or stratified squamous epithelium
marks Paget’s disease and extramammary Paget’s
CK7 use for what?
dtermine origin of metastatic carcinoma
marker for non-GI adenocarcinoma
Mark’s Paget’s disease and extramammary Paget’s
CK20 stains what tumor?
Merkel cell carcinoma - stains in paranuclear pattern and distinguishes from metastatic oat cell carcinoma of lung that is typically negative
used in determining origin of metastatic carcinoma
marker of rGI adenocarcinoma
highlights sparase Merkel cells within basaloid islands of desmoplastic trichoep but not BCC
CK7 +, CK20+
bladder, pancreatic
CK7+, CK20 -
breast, lung, mesothelioma
CK7-, CK20+
Colon cancer
CK7-, CK20-
hepatocellular, prostate, renal, neuroendocrine and SCC of lung
CK7 positive
(generally non-GI adenocarcinoma)
bladder, pancreatic (CK20+)
breast, lung, mesothelioma (CK20-)
CK20 positive
(generally positive in GI adenocarcinoma)
bladder, pancreatic (CK7+)
colon (CK7-)
CDX2 stains what
intestinal adenocarcinoma
cutaneous metastatic colon adenocarcinoma and extrammamary Paget’s a/w underlying colorectal tumor
RCC (renal cell carcinoma)
positive in most cutaneous mets from RCC and negative in other clear cell tumors of skin
TTF-1
thyroid transcription factor
reactive in metastatic small cell lung carcinoma but negative in Merkel cell carcinoma
EMA
epithelial membrane antigen
highlights normal sebaceous and sweat glands
positive in sebaceous carcinoma, Paget’s and extramammary Paget’s
CEA
carincoembryonic antigen
highlights sweat glands, sweat gland neoplasms, Paget’s, extrammamary Paget’s and most adenocarcinomas
adipophylin stains
lipid droplets of sebaceous and xanthomatous lesions
helps distinguish sebaceous carcinoma from SCC and BCC
Ber-EP4
marks most epithelial cells but not those with squamous differentiation
positive in BCC but negative in SCC
Desmin stains
sekeletal and most smooth muscle
negative in vascular smooth muscle including glomus cells
CD34 stains what normal structures
vascular endothelium and hematopoietic progenitor cells
positive in DFSP, negative in DF
positive in spindle cell lipoma, sclerotic fibroma, solitary fibrous tumor, superficial acral fibromyxoma, pleomorphic fibroma and pleomorphic hyalinizing angiectatic tumordecreased staining in morphea
increased staining in nephrogenic systemic fibrosis
stains connective tissue around normal hair folicles
typically hilights stroma of trichoeps but not BCCs
Factor 13a stains
DF, not DFSP
highlights dermal dendritic cells
positive in fibrous papule of hte face/angiofibroma
CD31 is a marker for
vascular origin of tumors
more specific for vascular than CD34
D2-40 (podoplanin) is a marker of
lymphatic endothelium
increases detection of lymphovascular invasion
lack of reactivity in metastatic carcinoma assiststs in differentiation from primary cutaneous adnexal neoplasms
UEA-1 *Ulex europeus agglutinin) binds
vascular endothlium
GLUT1 STAINS
endothelial cells with blood-tissue barrier functiona sin placenta
positive in infantile hemangiomas and negative in vascular malformations
also stains perineurial cells and perineurioma
Vimentin stains
general marker of sarcomas
stains mesenchymal cells, endothelial cells, fibroblasts, melanocytes, lymphocytes, macrophages
does not react with epithelium/keratinocytes
excludes most carcinomas except rare spindle cell carcinomas and synovial carcinoma
S100 stains
neural crest-derived cells and some mesenchymal lines
staines melanocytes, Langerhans cells, sweat glands, nerves, schwann cells, myoepithelial cells, fat, muscle and chondrocytes
useful in ddx of spindle cell neoplasms
stains desmoplastic melanoma, langerhans cell histiocytosis, granular cell tumor, Rosai-Dorfman disease
S100A6 (calcyclin) stains
member of S100 superfamily
positive in cellular neurothekeoma while S100 is negative
reactive in most atypical fibroxanthomas but not specific
also stains other spindle cell tumors
stains Spitz strongly and diffusely but spitzoid melanomas have weak or patchy staining
HMB-45 is a marker of
premelanosome
loss of stianing of melanocytes with descent into dermis is manifestation of loss of premalnoosomes, marker ofr normal maturation
loss of staining in deep dermal component of most benig nevi but get uniform staining of blue nevi
does not stain desmoplastic melanoma reliably
melan-A and Mart-1
2 different antibodfies stain same epitope
stain melanocytic lesions but staining of desmoplastic melanoma is unreliable
p75 (nerve growth factor receptor)
early neural crest cell marker
expressed in type C (spindled) melanocytes and schwann cells
sensitive marker for spindle cell and desmoplastic melanoma
MITF (micropthalmia-associated transcription factor)
essential in development and survival of melanocytes
nuclear melanocyte marker
positive in cellular neurothekeomas
Sox-10
nuclear marker of melanocytes and Schwann cells
sensitive marker of melanoma including conventional, spindled and desmoplastic
Neuron-specific enolase (NSE)
positive in neuroendocrine cells, neurons and tumors derived from them
fairly non-specific as positive in many other cell lines
Chromogranin positive in what tumor?
merkel cell carcinoma
synaptophysin positive in what tumor?
merkel cell carcinoma
CD45Ra (LCA)
leukocyte common antigen (LCA) general marker of hematolymphoid differentiation
present on all hematopoietic cells and precursors with exception of maturing erythroids and megakaryocytes
CD45Ro (UCHL-1)
stains mature T cells
CD20 stains
B cells (often absent in plasma cells)
positive in B cell lymphoma
target for rituximab
loss correlates with rituximab resistance
CD10 (CALLA)
common acute lymphoblastic leukemia antigen
early marker of B cell differentiation
useful for diagnosis of B cell lymphoproliferative disorders
positive in periadnexal mesenchymal cells, staining only stroma of trichoblastomas but epithelial cells of BCC
expressed in most atypical fibroxanthomas but not often seen in other spindle cell tumors
marker of renal cell carcinoma but also in other clear cell lesions including balloon cell nevi, clear cell hidradenoma and sebaceous tumors
CD79a marker for
plasma cell and B cell
CD138 (syndecan-1) stains
plasma cell marker
CD3 stains
T cells - pan -T-cell marker
CD4 stains
helper T cells
CD8 stains
cytotoxic/suppressor T cell marker
CD5 stains
pan-T cell marker but aberrant loss in CTCL is common
positive in mantle cell lymphoma and infiltrates of chronic lymphocytic leukemia
CD30 (Ki-1, BERH2) stains
Reed-Sternberg cells of Hodgkin’s disease
positive in activated lymphs of anaplastic large cell lymphoma and lymphomatoid papulosis
many positive cells may be seen in scabies nodules and chronic tick bites
CD7
immature T lymphocyte antigen
most common antigen lost in T cell lymphoma
CD56
marker of NK cells and subset of T cells
stains blastic plasmacytoid dendritic cell neoplasm (fomerly known as blastic NK/T-cell lymphoma or CD4+/CD56+ hematodermic neoplasm)
CD68 (KP-1)
reactive in virtually all monocyte/macrophage cells
CD163
reactive in monocytes and macrophages
CD123
marker of plasmacytoic dendritic cells
positive in blastic plasmacytoid dendritic cell neoplasm
myeloperoxidase
major constituent of granuleso f neutrophilic myeloid cells
marker for acute myeloid leukemia
ALK-1
anaplastic lymphoma kinase expressing chromosomal translocation t(2,5)
positive in most systemic anaplastic large cell lymphoma and negativ ein primary cutaneous anaplastic large cell lymphoma
few patients with ALK-1 negative systemic anaplastic large cell lymphoma have poor prognosis
Kappa/lambda
normally expressed in ratio f 2/3 kappa to 1/3 lambda
10 fold deviation suggests clonal B-cell proliferation
CD117 (c-Kit)
expressed in mast cells and melanocytes
in nevi and primary melanoma there is decrease in expression in dermal component
typically lost in metastatic cutaneous melanoma
CD1a
stains Langerhans cells
Langerin (CD207) stians
Birbeck granules in Langerhans cells
CD43 (Leu-22)
pan-T-cell marker
aberrant coexpression with CD20 strongly suggestive of B cell lymphoma
BCL2
onocogene that inhibits apoptosis
useful to differentiation B cell lymphoproliferative disorders
most BCCs have diffuse BCL2 staining wheras trichoeps only show staining of outermost epithelial layeres of tumor islands
MUM-1 (Multiple myelanoma oncogene-1)
expressed in plasma cells, activated T cells, and subset of germinal center cells
distinguishes primary cutaneous diffuse large B cell lymphoma, leg type from diffuse follicle center lymphoma
reactivity reported in anaplastic large cell lymphoma, LyP and blastic plasmacytoid dendritic cell neoplasm
also expressed in benign and malignant melanocytic cells
CD21
follicular dendritic cell marker
highlights residual follicle in lymphoma
CD23 has a similar staining pattern
betaF1
identified alphabeta T cells
Spindle cell neoplasms should be stianed with what?
pankeratin or AE1/AE3 - positive in SCC
CD10 - positive in atypical fibroxanthoma, may be positive in SCC, melanoma, leiomyosarcoma
S100/Sox-10 - positive in melanoma
Desmin - positive in leiomyosarcoma
small blue cell tumors should be stained with
LCA - positive in lymphoma
TTF-1 - positive in metastatic small cell carcinoma of lung, sometimes in lymphoma
CK20 - positive in Merkel cell carcinoma
Synaptophysin - positive in Merkel cell carcinoma, sometimes metatstatic small cell carcinoma of lung
S100 - positive in melanoma, sometimes merkel cell carcinoma
small round blue cell S100 positive
probably melanoma, could be merkel cell (get synaptophysin or CK20)
small round blue cell TTF-1 positive
probably metastatic small cell caricnoma of lung, could be lymphoma, get LCA (Positive in lymphoma)
small round blue tumor positive for synaptophysin
probably merkel cell but could be metastatic small cell carcinoma of the lung, get TTF-1 (positive in small cell carcinoma of lung)
What tumors have intraepidermal buckshot scatter (pagetoid spread)
Paget’s, extramammary Paget’s, Bowens, Malignant melanoma
for pagetoid scattered order what stains?
CK7 (positive in Paget’s and sometimes Bowens disease)
CEA (positive in Paget’s)
S100 (positive in melanoma)
specific immunohistochemical antibodies available to many viruses, bacterial, fungal and parasitic antigens including
HHV8, HSV, VZV, CMV, EBV, bartonella, Rickettsia, treponema, Borrelia, Aspergillus, Leishmania and others
markers of proliferation include
Mib-1 (Ki-67) - nuclear prolifereation marker expressedin all active phases of cell cycle
pHH3 - mitotic marker only stains M phase of cell cycle; helps differentiate mitoses from apoptotic or hyperchromatic nuclei
what transport media should be used for electron microscopy
glutaraldehyde
what transport medium should be used for immunofluorescence?
Michel’s medium (ammonium sulfate). if not available, use normal saline.
